Genetic Testing Policy Number: PG0041 ADVANTAGE | ELITE | HMO Last Review: 04/11/2021

INDIVIDUAL MARKETPLACE | PROMEDICA MEDICARE PLAN | PPO GUIDELINES This policy does not certify benefits or authorization of benefits, which is designated by each individual policyholder terms, conditions, exclusions and limitations contract. It does not constitute a contract or guarantee regarding coverage or reimbursement/payment. Paramount applies coding edits to all medical claims through coding logic software to evaluate the accuracy and adherence to accepted national standards. This medical policy is solely for guiding medical necessity and explaining correct procedure reporting used to assist in making coverage decisions and administering benefits.

SCOPE X Professional X Facility

DESCRIPTION A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to a heritable or acquired disorder. This can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing). Clinical genetic tests are those in which specimens are examined and results reported to the provider or patient for the purpose of diagnosis, prevention or treatment in the care of individual patients.

Genetic testing is performed for a variety of intended uses:  Diagnostic testing (to diagnose disease)  Predictive testing (generally performed to gather genetic data that can assist in clinical management, including therapeutic decision for an individual.  Pre-symptomatic genetic testing (to predict future disease)  Carrier testing (to identify carriers of genetic mutations)  Prenatal testing (offered during pregnancy to identify fetuses that have certain diseases)  Pre-implantation genetic testing (done in conjunction with invitro fertilization to determine whether embryos for implantation carry a gene mutation that could cause disease)  Newborn screening (to test newborns shortly after birth to determine whether they have certain diseases known to cause problems with health and development)  Pharmacogenetic testing (to determine the likelihood of an individual being responsive to a particular drug and/or to predict serious toxicity from a drug in order to optimize drug selection or drug dosage)  Research genetic testing (used to help with research and development of gene-based therapy)

Several hundred genetic tests are currently in use, and more are being developed. Although genetic testing can provide helpful information for diagnosing, treating, and preventing illness, there are limitations. For example, in a healthy patient, a positive result from a genetic test does not always mean the patient will develop a disease. On the other hand, in some situations, a negative result does not guarantee the patient will not have a certain disorder.

POLICY HMO, PPO, Individual Marketplace, Elite/ProMedica Medicare Plan, Advantage Paramount does not cover investigational or experimental medical or surgical procedures that are not medically necessary and have not been strongly supported in research and for which there is a safe and medically accepted alternative available.

PG0041 – 08/06/2021  Prior authorization is required for all genetic testing unless otherwise noted in one of the genetic specific policies (listed below), no matter the diagnosis.  Prior authorization is required for all Non-Par Providers for ALL genetic testing.

2021 new codes added to the medical policy along with coverage and prior authorizations determinations-see table below.  Procedure 0047U coverage change from Non-Covered to requires a Prior Authorization required for the Advantage Product line, effective 04/01/2021.

 Procedures 81168, 81191, 81192, 81193, 81194, 81351, 81353, require a prior authorization, ALL product lines, effective 04/01/2021.

 Procedures 81278, 81279, 81338, 81339, 81347, 81348, 81352, 81357, 81360, do not require a prior authorization, ALL product lines, effective 01/01/2021.

 Procedures 81554, 0173U, 0174U, 0175U, 0177U, 0179U, 0180U, 0181U, 0182U, 0183U, 0184U, 0185U, 0186U, 0187U, 0188U, 0189U, 0190U, 0191U, 0192U, 0193U, 0194U, 0195U, 0196U, 0197U, 0198U, 0199U, 0200U, 0201U, 0203U, 0204U, 0205U, 0208U, 0209U, 0211U, 0212U, 0213U, 0214U, 0215U, 0216U, 0217U, 0218U, 0220U, 0221U, 0222U, 0229U, 0230U, 0231U, 0232U, 0233U, 0234U, 0235U, 0236U, 0237U, 0238U, 0239U are Non-Covered, ALL product lines, effective 01/01/2021.

 Procedure 0172U requires a prior authorization for Commercial and Elite/ProMedica Medicare product lines, effective 04/01/2021. Procedure 0172U is Non-Covered, Advantage product line, effective 01/01/2021.

Some genetic testing requires prior authorization or may be non-covered. A provider must refer to the Paramount prior authorization list and specific medical policy in reference to specific tests for coverage determinations (this list may not be all-inclusive):  PG0065 Colorectal Cancer Screening (81327, 81401, 81528)  PG0067 Genetic Testing for Hereditary Breast and Ovarian Cancer Syndrome (HBOC) (81162, 81212, 81215, 81216, 81217, 81432, 81433)  PG0119 gene Expression Profiling of Melanomas (0089U, 0090U, 81401, 81529, 51552, 81479, 81599)  PG0280 Genetic Testing for Cardiac Conditions (81413, 81414, 81439, S3861-S3866)  PG0287 Non-Invasive Prenatal Screening (NIPS)/Cell-Free DNA Tests For Fetal Aneuploidy (81420, 81422, 81507, 0009M)  PG0296 Comparative Genomic Hybridization (CGH)/Chromosomal Microarray Analysis (CMA) (81228, 81229, S3870)  PG0298 Molecular Markers in Fine Needle Aspirates of Thyroid Nodules (81210, 81406, 81445, 81546, 81599, 0018U, 0026U, 0204U, 0208U, 0245U)  PG0301 Genetic Expression Assays for Breast Cancer Prognosis (81479, 81519, 81520, 81521, 0008M, S3854)  PG0302 Genetic Testing for Lynch Syndrome and Polyposis Syndromes (81201- 81203, 81288, 81292-81301, 81317-81319, 81401, 81403, 81406, 81435, 81436)  PG0336 PTEN Genetic Testing (81321-81323)  PG0340 AlloMap™ Molecular-Expression Blood Test (81595)  PG0355 Genetic Testing for Hereditary Thrombophilia (81240, 81241, 81291)  PG0357 Gene Expression Profiling for Colorectal Cancer (81525)  PG0358 Genetic Counseling  PG0360 Genetic Testing for Fragile X-Related Disorders (81243, 81244)  PG0362 Vectra® DA (81490)  PG0363 CORUS® CAD (81493)

PG0041 – 08/06/2021  PG0364 Gene Expression Profiling for Cancers of Unknown Primary Site (81504, 81540)  PG0367 Gene Expression Analysis for Prostate Cancer (81313, 81479, 81539, 81541, 81551)  PG0368 GeneSight® Assay for Refractory Depression (81479)  PG0375 Molecular Cytogenetic Testing (88230, 88233, 88235, 88237, 88239-88241, 88245, 88248, 88249, 88261-88264, 88267, 88269, 88271-88275, 88280, 88283, 88285, 88289, 88291, 88299)  PG0387 Genetic Testing for Cystic Fibrosis (81220-81224)  PG0390 Genetic Testing for Warfarin Dose (G9143, 81227, 81355)  PG0391 UGT1A1 Targeted Mutation Analysis for Irinotecan Response (81350)  PG0398 Genetic Testing for Spinal Muscular Atrophy (81329, 81336, 81337)  PG0411 Genetic Testing for Dystrophinopathies (Duchenne and Becker Muscular Dystrophy) (81161, 81408)  PG0412 Genetic Testing for Age-Related Macular Degeneration (81401, 81405, 81408, 81479, 81599)  PG0417 Proprietary Laboratory Analyses (PLA) Codes (0001U-0061U)  PG0436 CYP2C19 & CYP2D6 Pharmacogenetic Testing (81225, 81226)  PG0437 HLA-B1502 & HLA-B5701 Pharmacogenetic Testing (81381)  PG0438 Next Generation Sequencing (NGS) Tests for Advanced Cancer (81455, 81479)  PG0442 Carrier Screening for Genetic Diseases (81200, 81205, 81209, 81220, 81242, 81250, 81251-81255, 81257-81260, 81265, 81266, 81269, 81290, 81330, 81361, 81362-81364, 81400, 81401, 81403, 81404, 81406, 81412, 81443, 81479)  PG0453 Germline Multi-Gene Panel Genetic Testing (81410, 81411, 81412, 81413, 81414, 81415, 81416, 81417, 81419, 81420, 81422, 81425, 81426, 81427, 81430, 81431, 81432, 81433, 81434, 81435, 81436, 81437, 81438, 81439, 81440, 81442, 81443, 81445, 81448, 81450, 81455, 81460, 81465, 81470, 81471)  PG0467 Genetic Testing for Epilepsy (81188, 81189, 81190, 81401, 81403, 81404, 81405, 41406, 81407, 81419, 81479)  PG0468 Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS) (81415, 81416, 81417, 81425, 81426, 81427)

Refer to CODING/BILLING INFORMATION below for coverage determination.

COVERAGE CRITERIA HMO, PPO, Individual Marketplace, Elite/ProMedica Medicare Plan, Advantage Coverage and authorization for genetic testing is determined by review. The testing must have direct effect on the management and clinical care of the individual being tested, and must contain all of the following criteria:  Individual has not previously received genetic testing for the disorder. In general, genetic testing for a particular disorder should be performed once per lifetime; however, there are rare instances in which testing may be performed more than once in a lifetime (e.g., previous testing methodology is inaccurate, a new discovery has added significant relevant mutations for a disease, significant changes in technology or treatments indicate that test results or outcomes may change as a result of repeat testing)  The genetic disorder is associated with a significant disability or has a lethal natural history  The risk of the significant disability or lethality from the genetic disorder cannot be determined through other diagnostic testing  A specific mutation, or set of mutations, has been proven valid in the scientific literature to be reliable, associated with the disease  The results of the genetic test could impact the medical management of the individual being tested  The genetic test will likely result in an anticipated improvement in net health outcomes for the individual being tested (i.e., the disease is treatable or preventable)  Panels including, but may not limited to, multiple genes or multiple conditions, and in cases where a tiered approach/method is clinically available, may be covered ONLY for the number of genes or tests deemed medically necessary to establish a diagnosis

When requesting prior authorization review, the patient’s medical history/record and details of the lab facility providing the requested service must be provided. An approved request will only be given to a specific lab for a

PG0041 – 08/06/2021 specific provider for a specific service. Genetic testing may be denied as experimental or not medically necessary based on the information submitted.

The physician, lab or facility ordering the service will be financially responsible if prior authorization is not obtained. Members who choose to precede with unauthorized genetic testing bear the responsibility for the cost. The provider should always secure a Waiver of Responsibility prior to providing the testing to assure member understanding of their financial responsibility.

CODING/BILLING INFORMATION The appearance of a code in this section does not necessarily indicate coverage. Codes that are covered may have selection criteria that must be met. Payment for supplies may be included in payment for other services rendered.

HMO, PPO, Elite/ProMedica CPT CODES Individual Advantage Medicare Plan Marketplace Tier 1 Molecular Pathology Procedures Human Platelet Antigen 1 genotyping (HPA- 1), ITGB3 (integrin, beta 3 [platelet Prior Prior Prior glycoprotein IIIa], antigen CD61 [GPIIIa]) 81105 Authorization Authorization Authorization (eg, neonatal alloimmune thrombocytopenia required required required [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-1a/b (L33P) Human Platelet Antigen 2 genotyping (HPA- 2), GP1BA (glycoprotein Ib [platelet], alpha Prior Prior Prior polypeptide [GPIba]) (eg, neonatal 81106 Authorization Authorization Authorization alloimmune thrombocytopenia [NAIT], required required required posttransfusion purpura), gene analysis, common variant, HPA-2a/b (T145M) Human Platelet Antigen 3 genotyping (HPA- 3), ITGA2B (integrin, alpha 2b [platelet glycoprotein IIb of IIb/IIIa complex], antigen Prior Prior Prior 81107 CD41 [GPIIb]) (eg, neonatal alloimmune Authorization Authorization Authorization thrombocytopenia [NAIT], post- transfusion required required required purpura), gene analysis, common variant, HPA-3a/b (I843S) Human Platelet Antigen 4 genotyping (HPA- 4), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) Prior Prior Prior 81108 (eg, neonatal alloimmune thrombocytopenia Authorization Authorization Authorization [NAIT], post-transfusion purpura), gene required required required analysis, common variant, HPA-4a/b (R143Q) Human Platelet Antigen 5 genotyping (HPA- 5), ITGA2 (integrin, alpha 2 [CD49B, alpha 2 subunit of VLA-2 receptor] [GPIa]) (eg, Prior Prior Prior 81109 neonatal alloimmune thrombocytopenia Authorization Authorization Authorization [NAIT], post-transfusion purpura), gene required required required analysis, common variant (eg, HPA-5a/b (K505E)) Human Platelet Antigen 6 genotyping (HPA- 6w), ITGB3 (integrin, beta 3 [platelet Prior Prior Prior 81110 glycoprotein IIIa, antigen CD61] [GPIIIa]) Authorization Authorization Authorization (eg, neonatal alloimmune thrombocytopenia required required required [NAIT], post-transfusion purpura), gene

PG0041 – 08/06/2021 analysis, common variant, HPA-6a/b (R489Q) Human Platelet Antigen 9 genotyping (HPA- 9w), ITGA2B (integrin, alpha 2b [platelet glycoprotein IIb of IIb/IIIa complex, antigen Prior Prior Prior 81111 CD41] [GPIIb]) (eg, neonatal alloimmune Authorization Authorization Authorization thrombocytopenia [NAIT], post- transfusion required required required purpura), gene analysis, common variant, HPA-9a/b (V837M) Human Platelet Antigen 15 genotyping (HPA-15), CD109 (CD109 molecule) (eg, Prior Prior Prior 81112 neonatal alloimmune thrombocytopenia Authorization Authorization Authorization [NAIT], post-transfusion purpura), gene required required required analysis, common variant, HPA-15a/b IDH1 (isocitrate dehydrogenase 1 [NADP+], Prior Prior Prior 81120 soluble) (eg, glioma), common variants (eg, Authorization Authorization Authorization R132H, R132C) Not required Not required Not required IDH2 (isocitrate dehydrogenase 2 [NADP+], Prior Prior Prior 81121 mitochondrial) (eg, glioma), common Authorization Authorization Authorization variants (eg, R140W, R172M) Not required Not required Not required DMD (dystrophin) (e.g., Duchenne/Becker PG0411 Genetic Testing for 81161 muscular dystrophy) deletion analysis, and Dystrophinopathies (Duchenne and Becker duplication analysis, if performed Muscular Dystrophy) BRCA1, BRCA2 (breast cancer 1 and 2) (eg, hereditary breast and ovarian cancer) gene PG0067 Genetic Testing for Hereditary Breast 81162 analysis; full sequence analysis and full and Ovarian Cancer syndrome (HBOC) duplication/deletion analysis BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) PG0067 Genetic Testing for Hereditary Breast 81163 (eg, hereditary breast and ovarian cancer) and Ovarian Cancer syndrome (HBOC) gene analysis; full sequence analysis BRCA1, BRCA2 (breast cancer 1 and 2) (eg, PG0067 Genetic Testing for Hereditary Breast 81164 hereditary breast and ovarian cancer) gene and Ovarian Cancer syndrome (HBOC) analysis; full sequence analysis BRCA1 (BRCA1, DNA repair associated) PG0067 Genetic Testing for Hereditary Breast 81165 (eg, hereditary breast and ovarian cancer) and Ovarian Cancer syndrome (HBOC)) gene analysis; full sequence analysis BRCA1 (BRCA1, DNA repair associated) (eg, hereditary breast and ovarian cancer) PG0067 Genetic Testing for Hereditary Breast 81166 gene analysis; full duplication/deletion and Ovarian Cancer syndrome (HBOC) analysis (ie, detection of large gene rearrangements) BRCA2 (BRCA2, DNA repair associated) (eg, hereditary breast and ovarian cancer) PG0067 Genetic Testing for Hereditary Breast 81167 gene analysis; full duplication/deletion and Ovarian Cancer syndrome (HBOC) analysis (ie, detection of large gene rearrangements) CCND1/IGH (t(11;14)) (eg, mantle cell Prior Prior Prior lymphoma) translocation analysis, major 81168 Authorization Authorization Authorization breakpoint, qualitative and quantitative, if required required required performed ABL1 (ABL proto-oncogene 1, non-receptor Prior Prior Prior tyrosine kinase) (eg, acquired imatinib 81170 Authorization Authorization Authorization tyrosine kinase inhibitor resistance), gene Not required Not required Not required analysis, variants in the kinase domain

PG0041 – 08/06/2021 AFF2 (AF4/FMR2 family, member 2 [FMR2]) Prior Prior Prior 81171 gene analysis; evaluation to dtect abnormal Authorization Authorization Authorization (eg, expanded) alleles required required required AFF2 (AF4/FMR2 family, member 2 [FMR2]) Prior Prior Prior (eg, fragile X mental retardation 2 [FRAXE]) 81172 Authorization Authorization Authorization gene analysis; characterization of alleles (eg, required required required expanded size and methylation status) AR (androgen receptor) (eg, spinal and Prior Prior Prior bulbar muscular atrophy, Kennedy disease, 81173 Authorization Authorization Authorization X chromosome inactivation) gene analysis; required required required full gene sequence AR (androgen receptor) (eg, spinal and bulbar muscular atrophy, Kennedy disease, Prior Prior Prior 81174 X chromosome inactivation) gene analysis; Authorization Authorization Authorization known familial variant required required required

ASXL1 (additional sex combs like 1, transcriptional regulator) (eg, Prior Prior Prior myelodysplastic syndrome, 81175 Authorization Authorization Authorization myeloproliferative neoplasms, chronic required required required myelomonocytic leukemia), gene analysis; full gene sequence ASXL1 (additional sex combs like 1, transcriptional regulator) (eg, Prior Prior Prior myelodysplastic syndrome, 81176 Authorization Authorization Authorization myeloproliferative neoplasms, chronic required required required myelomonocytic leukemia), gene analysis; targeted sequence analysis (eg, exon 12) ATN1 (atrophin 1) (eg, dentatorubral- Prior Prior Prior pallidoluysian atrophy) gene analysis, 81177 Authorization Authorization Authorization evaluation to detect abnormal (eg, required required required expanded) alleles ATXN1 (ataxin 1) (eg, spinocerebellar Prior Prior Prior 81178 ataxia) gene analysis, evaluation to detect Authorization Authorization Authorization abnormal (eg, expanded) alleles required required required ATXN2 (ataxin 2) (eg, spinocerebellar Prior Prior Prior 81179 ataxia) gene analysis, evaluation to detect Authorization Authorization Authorization abnormal (eg, expanded) alleles required required required ATXN3 (ataxin 3) (eg, spinocerebellar ataxia, Prior Prior Prior Machado-Joseph disease) gene analysis, 81180 Authorization Authorization Authorization evaluation to detect abnormal (eg, required required required expanded) ATXN7 (ataxin 7) (eg, spinocerebellar Prior Prior Prior 81181 ataxia) gene analysis, evaluation to detect Authorization Authorization Authorization abnormal (eg, expanded) alleles required required required ATXN8OS (ATXN8 opposite strand [non- Prior Prior Prior protein coding]) (eg, spinocerebellar ataxia) 81182 Authorization Authorization Authorization gene analysis, evaluation to detect abnormal required required required (eg, expanded) alleles ATXN10 (ataxin 10) (eg, spinocerebellar Prior Prior Prior 81183 ataxia) gene analysis, evaluation to detect Authorization Authorization Authorization abnormal (eg, expanded) alleles required required required CACNA1A (calcium voltage-gated channel Prior Prior Prior 81184 subunit alpha1 A) (eg, spinocerebellar Authorization Authorization Authorization required required required

PG0041 – 08/06/2021 ataxia) gene analysis; evaluation to detect abnormal (eg, expanded) alleles CACNA1A (calcium voltage-gated channel Prior Prior Prior 81185 subunit alpha1 A) (eg, spinocerebellar Authorization Authorization Authorization ataxia) gene analysis; full gene sequence required required required CACNA1A (calcium voltage-gated channel Prior Prior Prior 81186 subunit alpha1 A) (eg, spinocerebellar Authorization Authorization Authorization ataxia) gene analysis; known familial variant required required required CNBP (CCHC-type zinc finger nucleic acid Prior Prior Prior binding protein) (eg, myotonic dystrophy type 81187 Authorization Authorization Authorization 2) gene analysis, evaluation to detect required required required abnormal (eg, expanded) alleles CSTB (cystatin B) (eg, Unverricht-Lundborg Prior Authorization required PG0467 Genetic 81188 disease) gene analysis; evaluation to detect Testing for Epilepsy abnormal (eg, expanded) alleles CSTB (cystatin B) (eg, Unverricht-Lundborg Prior Authorization required PG0467 Genetic 81189 disease) gene analysis; full gene sequence Testing for Epilepsy CSTB (cystatin B) (eg, Unverricht-Lundborg Prior Authorization required PG0467 Genetic 81190 disease) gene analysis; known familial Testing for Epilepsy variant(s) NTRK1 (neurotrophic receptor tyrosine Prior Prior Prior 81191 kinase 1) (eg, solid tumors) translocation Authorization Authorization Authorization analysis required required required NTRK2 (neurotrophic receptor tyrosine Prior Prior Prior 81192 kinase 2) (eg, solid tumors) translocation Authorization Authorization Authorization analysis required required required NTRK3 (neurotrophic receptor tyrosine Prior Prior Prior 81193 kinase 3) (eg, solid tumors) translocation Authorization Authorization Authorization analysis required required required NTRK (neurotrophic-tropomyosin receptor Prior Prior Prior 81194 tyrosine kinase 1, 2, and 3) (eg, solid Authorization Authorization Authorization tumors) translocation analysis required required required ASPA (aspartoacylase) (e.g., Canavan Prior Prior 81200 disease) gene analysis, common variants Authorization Non-Covered Authorization (e.g., E285A, Y231X) required required APC (adenomatous polyposis coli) (e.g., familial adenomatosis polyposis [FAP], PG0302 Genetic Testing for Lynch Syndrome 81201 attenuated FAP) gene analysis; full gene and Polyposis Syndromes sequence APC (adenomatous polyposis coli) (e.g., familial adenomatosis polyposis [FAP], PG0302 Genetic Testing for Lynch Syndrome 81202 attenuated FAP) gene analysis; known and Polyposis Syndromes familial variants APC (adenomatous polyposis coli) (e.g., familial adenomatosis polyposis [FAP], PG0302 Genetic Testing for Lynch Syndrome 81203 attenuated FAP) gene analysis; and Polyposis Syndromes duplication/deletion variants AR (androgen receptor) (eg, spinal and bulbar muscular atrophy, Kennedy disease, Prior Prior Prior 81204 X chromosome inactivation) gene analysis; Authorization Authorization Authorization characterization of alleles (eg, expanded required required required size or methylation status) BCKDHB (branched-chain keto acid Prior Prior 81205 dehydrogenase E1, beta polypeptide) (e.g., Authorization Non-Covered Authorization Maple syrup urine disease) gene analysis, required required

PG0041 – 08/06/2021 common variants (e.g., R183P, G278S, E422X) BCR/ABL1 (t(9;22)) (e.g., chronic Prior Prior Prior myelogenous leukemia) translocation 81206 Authorization Authorization Authorization analysis; major breakpoint, qualitative or Not required Not required Not required quantitative BCR/ABL1 (t(9;22)) (e.g., chronic Prior Prior Prior myelogenous leukemia) translocation 81207 Authorization Authorization Authorization analysis; minor breakpoint, qualitative or Not required Not required Not required quantitative BCR/ABL1 (t(9;22)) (e.g., chronic Prior Prior Prior myelogenous leukemia) translocation 81208 Authorization Authorization Authorization analysis; other breakpoint, qualitative or Not required Not required Not required quantitative BLM (Bloom syndrome, RecQ helicase-like) Prior Prior 81209 (e.g., Bloom syndrome) gene analysis, Authorization Non-Covered Authorization 2281del6ins7 variant required required BRAF (B-Raf proto-oncogene, Prior Prior Prior 81210 serine/threonine kinase) (e.g., colon cancer, Authorization Authorization Authorization melanoma), gene analysis, V600 variant(s) Not required Not required Not required BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) PG0067 Genetic Testing for Hereditary Breast 81212 gene analysis; 185delAG, 5385insC, and Ovarian Cancer Syndrome 6174delT variants BRCA1 (breast cancer 1) (e.g., hereditary PG0067 Genetic Testing for Hereditary Breast 81215 breast and ovarian cancer) gene analysis; and Ovarian Cancer Syndrome known familial variant BRCA2 (breast cancer 2) (e.g., hereditary PG0067 Genetic Testing for Hereditary Breast 81216 breast and ovarian cancer) gene analysis; and Ovarian Cancer Syndrome full sequence analysis BRCA2 (breast cancer 2) (e.g., hereditary PG0067 Genetic Testing for Hereditary Breast 81217 breast and ovarian cancer) gene analysis; and Ovarian Cancer Syndrome known familial variant CEBPA (CCAAT/enhancer binding protein Prior Prior Prior 81218 [C/EBP], alpha) (eg, acute myeloid Authorization Authorization Authorization leukemia), gene analysis, full gene sequence Not required Not required Not required CALR (calreticulin) (eg, myeloproliferative Prior Prior Prior 81219 disorders), gene analysis, common variants Authorization Authorization Authorization in exon 9 Not required Not required Not required CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) 81220 PG0387 Genetic Testing for Cystic Fibrosis gene analysis; common variants (e.g., ACMG/ACOG guidelines) CFTR (cystic fibrosis transmembrane 81221 conductance regulator) (e.g., cystic fibrosis) PG0387 Genetic Testing for Cystic Fibrosis gene analysis; known familial variants CFTR (cystic fibrosis transmembrane 81222 conductance regulator) (e.g., cystic fibrosis) PG0387 Genetic Testing for Cystic Fibrosis gene analysis; duplication/deletion variants CFTR (cystic fibrosis transmembrane 81223 conductance regulator) (e.g., cystic fibrosis) PG0387 Genetic Testing for Cystic Fibrosis gene analysis; full gene sequence CFTR (cystic fibrosis transmembrane 81224 PG0387 Genetic Testing for Cystic Fibrosis conductance regulator) (e.g., cystic fibrosis)

PG0041 – 08/06/2021 gene analysis; intron 8 poly-T analysis (e.g., male infertility) CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (e.g., drug PG0436 CYP2C19 & CYP2D6 Pharmacogenetic 81225 metabolism), gene analysis, common Testing variants (e.g., *2, *3, *4, *8, *17) CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (e.g., drug metabolism), gene analysis, common PG0436 CYP2C19 & CYP2D6 Pharmacogenetic 81226 variants (e.g., *2, *3, *4, *5, *6, *9, Testing *10, *17, *19, *29, *35, *41, *1XN, *2XN, *4XN) CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (e.g., drug 81227 PG0390 Genetic Testing for Warfarin Dose metabolism), gene analysis, common variants (e.g., *2, *3, *5, *6) Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic PG0296 Comparative Genomic Hybridization regions for copy number variants (e.g., 81228 (CGH)/Chromosomal Microarray Analysis Bacterial Artificial Chromosome [BAC] or (CMA) oligo-based comparative genomic hybridization [CGH] microarray analysis) Cytogenomic constitutional (genome-wide) PG0296 Comparative Genomic Hybridization microarray analysis; interrogation of genomic (CGH)/Chromosomal Microarray Analysis 81229 regions for copy number and single (CMA) nucleotide polymorphism (SNP) variants for chromosomal abnormalities CYP3A4 (cytochrome P450 family 3 Prior subfamily A member 4) (eg, drug 81230 Non-Covered Non-Covered Authorization metabolism), gene analysis, common required variant(s) (eg, *2, *22) CYP3A5 (cytochrome P450 family 3 Prior subfamily A member 5) (eg, drug 81231 Non-Covered Non-Covered Authorization metabolism), gene analysis, common required variants (eg, *2, *3, *4, *5 *6, *7) DPYD (dihydropyrimidine dehydrogenase) (eg, 5- fluorouracil/5-FU and capecitabine Prior 81232 drug metabolism), gene analysis, common Non-Covered Non-Covered Authorization variant(s) (eg, *2A, *4, *5, required *6) (Effective 01/01/2018 new code) BTK (Bruton's tyrosine kinase) (eg, chronic Prior Prior Prior lymphocytic leukemia) gene analysis, 81233 Authorization Authorization Authorization common variants (eg, C481S, C481R, Not required Not required Not required C481F) DMPK (DM1 protein kinase) (eg, myotonic Prior Prior Prior 81234 dystrophy type 1) gene analysis; evaluation Authorization Authorization Authorization to detect abnormal (expanded) alleles required required required EGFR (epidermal growth factor receptor) (e.g., non- small cell lung cancer) gene Prior Prior Prior 81235 analysis, common variants (e.g., exon 19 Authorization Authorization Authorization LREA deletion, L858R, T790M, G719A, required required required G719S, L861Q) (LCD L32288) EZH2 (enhancer of zeste 2 polycomb Prior Prior Prior 81236 repressive complex 2 subunit) (eg, Authorization Authorization Authorization myelodysplastic syndrome, Not required Not required Not required

PG0041 – 08/06/2021 myeloproliferative neoplasms) gene analysis, full gene sequence EZH2 (enhancer of zeste 2 polycomb Prior Prior Prior repressive complex 2 subunit) (eg, diffuse 81237 Authorization Authorization Authorization large B-cell lymphoma) gene analysis, Not required Not required Not required common variant(s) (eg, codon 646) F9 (coagulation factor IX) (eg, hemophilia B), Prior Prior Prior 81238 full gene sequence Authorization Authorization Authorization required required required DMPK (DM1 protein kinase) (eg, myotonic Prior Prior Prior dystrophy type 1) gene analysis; 81239 Authorization Authorization Authorization characterization of alleles (eg, expanded required required required size) F2 (prothrombin, coagulation factor II) (e.g., PG0355 Genetic Testing for Hereditary 81240 hereditary hypercoagulability) gene analysis, Thrombophilia 20210G>A variant F5 (coagulation Factor V) (e.g., hereditary PG0355 Genetic Testing for Hereditary 81241 hypercoagulability) gene analysis, Leiden Thrombophilia variant FANCC (Fanconi anemia, complementation Prior Prior group C) (e.g., Fanconi anemia, type C) 81242 Authorization Non-Covered Authorization gene analysis, common variant (e.g., required required IVS4+4A>T) FMR1 (Fragile X mental retardation 1) (e.g., fragile X mental retardation) gene analysis; PG0360 Genetic Testing for Fragile X-Related 81243 evaluation to detect abnormal (e.g., Disorders expanded) alleles FMR1 (Fragile X mental retardation 1) (e.g., fragile X mental retardation) gene analysis; PG0360 Genetic Testing for Fragile X-Related 81244 characterization of alleles (e.g., expanded Disorders size and methylation status) FLT3 (fms-related tyrosine kinase 3) (eg, Prior Prior Prior acute myeloid leukemia), gene analysis; 81245 Authorization Authorization Authorization internal tandem duplication (ITD) variants Not required Not required Not required (i.e., exons 14, 15) FLT3 (fms-related tyrosine kinase 3) (eg, Prior Prior Prior acute myeloid leukemia), gene analysis; 81246 Authorization Authorization Authorization tyrosine kinase domain (TKD) variants (eg, Not required Not required Not required D835, I836) G6PD (glucose-6-phosphate Prior Prior Prior dehydrogenase) (eg,hemolytic anemia, 81247 Authorization Authorization Authorization jaundice), gene analysis; common variant(s) required required required (eg, A, A-) G6PD (glucose-6-phosphate Prior Prior Prior dehydrogenase) (eg,hemolytic anemia, 81248 Authorization Authorization Authorization jaundice), gene analysis; known familial required required required variant(s) G6PD (glucose-6-phosphate Prior Prior Prior 81249 dehydrogenase) (eg,hemolytic anemia, Authorization Authorization Authorization jaundice), gene analysis; full gene sequence required required required G6PC (glucose-6-phosphatase, catalytic Prior Prior subunit) (e.g., Glycogen storage disease, 81250 Authorization Non-Covered Authorization Type 1a, von Gierke disease) gene analysis, required required common variants (e.g., R83C, Q347X)

PG0041 – 08/06/2021 GBA (glucosidase, beta, acid) (e.g., Gaucher Prior Prior 81251 disease) gene analysis, common variants Authorization Non-Covered Authorization (e.g., N370S, 84GG, L444P, IVS2+1G>A) required required GJB2 (gap junction protein, beta 2, 26kDa, Prior Prior connexin 81252 Authorization Non-Covered Authorization 26) (e.g., nonsyndromic hearing loss) gene required required analysis; full gene sequence (LCD L32288) GJB2 (gap junction protein, beta 2, 26kDa; connexin Prior Prior 81253 26) (e.g., nonsyndromic hearing loss) gene Authorization Non-Covered Authorization analysis; known familial variants (LCD required required L32288) GJB6 (gap junction protein, beta 6, 30kDa, connexin Prior Prior 30) (e.g., nonsyndromic hearing loss) gene 81254 Authorization Non-Covered Authorization analysis, common variants (e.g., 309kb required required [del(GJB6- D13S1830)] and 232kb [del(GJB6-D13S1854)]) (LCD L32288) HEXA (hexosaminidase A [alpha Prior Prior polypeptide]) (e.g., Tay-Sachs disease) gene 81255 Authorization Non-Covered Authorization analysis, common variants(e.g., required required 1278insTATC, 1421+1G>C, G269S) HFE (hemochromatosis) (e.g., hereditary Prior Prior Prior 81256 hemochromatosis) gene analysis, common Authorization Authorization Authorization variants (e.g., C282Y, H63D) Not required Not required Not required HBA1/HBA2 (alpha globin 1 and alpha globin 2) (e.g., alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene Prior Prior 81257 analysis; common deletions or variant (e.g., Authorization Non-Covered Authorization Southeast Asian, Thai, Filipino, required required Mediterranean, alpha3.7, alpha4.2, alpha20.5, and Constant Spring) HBA1/HBA2 (alpha globin 1 and alpha globin Prior Prior 2) (e.g., alpha thalassemia, Hb Bart hydrops 81258 Authorization Non-Covered Authorization fetalis syndrome, HbH disease), gene required required analysis; known familial variant HBA1/HBA2 (alpha globin 1 and alpha globin Prior Prior 2) (e.g., alpha thalassemia, Hb Bart hydrops 81259 Authorization Non-Covered Authorization fetalis syndrome, HbH disease), gene required required analysis; full gene sequence IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex- Prior Prior 81260 associated protein) (e.g., familial Authorization Non-Covered Authorization dysautonomia) gene analysis, common required required variants (e.g., 2507+6T>C, R696P) IGH@ (Immunoglobulin heavy chain locus) (e.g., leukemias and lymphomas, B-cell), Prior Prior Prior gene rearrangement analysis to detect 81261 Authorization Authorization Authorization abnormal clonal population(s); amplified Not required Not required Not required methodology (e.g., polymerase chain reaction) IGH@ (Immunoglobulin heavy chain locus) Prior Prior Prior 81262 (e.g., leukemias and lymphomas, B-cell), Authorization Authorization Authorization gene rearrangement analysis to detect Not required Not required Not required

PG0041 – 08/06/2021 abnormal clonal population(s); direct probe methodology (e.g., Southern blot) IGH@ (Immunoglobulin heavy chain locus) Prior Prior Prior 81263 (e.g., leukemia and lymphoma, B-cell), Authorization Authorization Authorization variable region somatic mutation analysis Not required Not required Not required IGK@ (Immunoglobulin kappa light chain locus) (e.g., leukemia and lymphoma, B- Prior Prior Prior 81264 cell), gene rearrangement analysis, Authorization Authorization Authorization evaluation to detect abnormal clonal Not required Not required Not required population(s) Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (e.g., pre-transplant recipient and donor germline testing, post- Prior Prior Prior 81265 transplant non-hematopoietic recipient Authorization Authorization Authorization germline [e.g., buccal swab or other germline Not required Not required Not required tissue sample] and donor testing, twin zygosity testing, or maternal cell contamination of fetal cells) Comparative analysis using Short Tandem Repeat (STR) markers; each additional specimen (e.g., additional cord blood donor, Prior Prior Prior 81266 additional fetal samples from different Authorization Authorization Authorization cultures, or additional zygosity in multiple Not required Not required Not required birth pregnancies) (List separately in addition to code for primary procedure) Chimerism (engraftment) analysis, post transplantation specimen (e.g., Prior Prior Prior 81267 hematopoietic stem cell), includes Authorization Authorization Authorization comparison to previously performed baseline Not required Not required Not required analyses; without cell selection Chimerism (engraftment) analysis, post transplantation specimen (e.g., Prior Prior Prior hematopoietic stem cell), includes 81268 Authorization Authorization Authorization comparison to previously performed baseline Not required Not required Not required analyses; with cell selection (e.g., CD3, CD33), each cell type HBA1/HBA2 (alpha globin 1 and alpha globin Prior Prior 2) (eg, alpha thalassemia, Hb Bart hydrops 81269 Authorization Non-Covered Authorization fetalis syndrome, HbH disease), gene required required analysis duplication/deletion variants JAK2 (Janus kinase 2) (e.g., Prior Prior Prior 81270 myeloproliferative disorder) gene analysis, Authorization Authorization Authorization p.Val617Phe (V617F) variant NOT required NOT required NOT required HTT (huntingtin) (eg, Huntington disease) Prior 81271 gene analysis; evaluation to detect abnormal Non-Covered Non-Covered Authorization (eg, expanded) alleles required KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (eg, gastrointestinal Prior Prior Prior stromal tumor [GIST], acute myeloid 81272 Authorization Authorization Authorization leukemia, melanoma), gene analysis, NOT required NOT required NOT required targeted sequence analysis (eg, exons 8, 11, 13, 17, 18)

PG0041 – 08/06/2021 KIT (v-kit Hardy-Zuckerman 4 feline sarcoma Prior Prior Prior 81273 viral oncogene homolog) (eg, mastocytosis), Authorization Authorization Authorization gene analysis, D816 variant(s) NOT required NOT required NOT required HTT (huntingtin) (eg, Huntington disease) Prior 81274 gene analysis; characterization of alleles (eg, Non-Covered Non-Covered Authorization expanded size) required KRAS (Kirsten rat sarcoma viral oncogene Prior Prior Prior 81275 homolog) (e.g., carcinoma) gene analysis, Authorization Authorization Authorization variants in exon 2 (eg, codons 12 and 13) NOT required NOT required NOT required (KRAS (Kirsten rat sarcoma viral oncogene Prior Prior Prior homolog) (eg, carcinoma) gene analysis; 81276 Authorization Authorization Authorization additional variant(s) (eg, codon 61, codon NOT required NOT required NOT required 146) Cytogenomic neoplasia (genome-wide) microarray analysis, interrogation of genomic Prior Prior Prior 81277 regions for copy number and loss-of- Authorization Authorization Authorization heterozygosity variants for chromosomal required required required abnormalities IGH@/BCL2 (t(14;18)) (eg, follicular lymphoma) translocation analysis, major No Prior No Prior No Prior 81278 breakpoint region (MBR) and minor cluster Authorization Authorization Authorization region (mcr) breakpoints, qualitative or required required required quantitative JAK2 (Janus kinase 2) (eg, No Prior No Prior No Prior 81279 myeloproliferative disorder) targeted Authorization Authorization Authorization sequence analysis (eg, exons 12 and 13) required required required IFNL3 (interferon, lambda 3) (eg, drug Prior Prior Prior 81283 response), gene analysis, rs12979860 Authorization Authorization Authorization variant required required required FXN (frataxin) (eg, Friedreich ataxia) gene Prior Prior Prior 81284 analysis; evaluation to detect abnormal Authorization Authorization Authorization (expanded) alleles required required required FXN (frataxin) (eg, Friedreich ataxia) gene Prior Prior Prior 81285 analysis; characterization of alleles (eg, Authorization Authorization Authorization expanded size) required required required FXN (frataxin) (eg, Friedreich ataxia) gene Prior Prior Prior 81286 analysis; full gene sequence Authorization Authorization Authorization required required required MGMT (O-6-methylguanine-DNA Prior Prior Prior 81287 methyltransferase) (e.g., glioblastoma Authorization Authorization Authorization multiforme), methylation analysis required required required LH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non- Prior Prior Prior 81288 polyposis colorectal cancer, Lynch Authorization Authorization Authorization syndrome) gene analysis; promoter required required required methylation analysis FXN (frataxin) (eg, Friedreich ataxia) gene Prior Prior Prior 81289 analysis; known familial variant(s) Authorization Authorization Authorization required required required MCOLN1 (mucolipin 1) (e.g., Mucolipidosis, Prior Prior 81290 type IV) gene analysis, common variants Authorization Non-Covered Authorization (e.g., IVS3-2A>G, del6.4kb) required required MTHFR (5,10-methylenetetrahydrofolate PG0355 Genetic Testing for Hereditary 81291 reductase) (e.g., hereditary Thrombophilia

PG0041 – 08/06/2021 hypercoagulability) gene analysis, common variants (e.g., 677T, 1298C) MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81292 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; full sequence analysis MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81293 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; known familial variants MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81294 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; duplication/deletion variants MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81295 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; full sequence analysis MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81296 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; known familial variants MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81297 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; duplication/deletion variants MSH6 (mutS homolog 6 [E. coli]) (e.g. hereditary non-polyposis colorectal cancer, PG0302 Genetic Testing for Lynch Syndrome 81298 Lynch syndrome) gene analysis; full and Polyposis Syndromes sequence analysis MSH6 (mutS homolog 6 [E. coli]) (e.g., hereditary non-polyposis colorectal cancer, PG0302 Genetic Testing for Lynch Syndrome 81299 Lynch syndrome) gene analysis; known and Polyposis Syndromes familial variants MSH6 (mutS homolog 6 [E. coli]) (e.g., hereditary non-polyposis colorectal cancer, PG0302 Genetic Testing for Lynch Syndrome 81300 Lynch syndrome) gene analysis; and Polyposis Syndromes duplication/deletion variants Microsatellite instability analysis (e.g., hereditary non-polyposis colorectal cancer, Prior Prior Prior Lynch syndrome) of markers for mismatch 81301 Authorization Authorization Authorization repair deficiency (e.g., BAT25, BAT26), required required required includes comparison of neoplastic and normal tissue, if performed MECP2 (methyl CpG binding protein 2) (e.g., Prior Prior 81302 Rett syndrome) gene analysis; full sequence Authorization Non-Covered Authorization analysis required required

PG0041 – 08/06/2021 MECP2 (methyl CpG binding protein 2) (e.g., Prior Prior 81303 Rett syndrome) gene analysis; known Authorization Non-Covered Authorization familial variant required required MECP2 (methyl CpG binding protein 2) (e.g., Prior Prior 81304 Rett syndrome) gene analysis; duplication/ Authorization Non-Covered Authorization deletion variants required required MYD88 (myeloid differentiation primary response 88) (eg, Waldenstrom's Prior Prior Prior 81305 macroglobulinemia, lymphoplasmacytic Authorization Authorization Authorization leukemia) gene analysis, p.Leu265Pro required required required (L265P) variant NUDT15 (nudix hydrolase 15) (eg, drug Prior Prior Prior 81306 metabolism) gene analysis, common Authorization Authorization Authorization variant(s) (eg, *2, *3, *4, *5, *6) required required required PALB2 (partner and localizer of BRCA2) (eg, Prior Prior Prior 81307 breast and pancreatic cancer) gene analysis; Authorization Authorization Authorization full gene sequence required required required PALB2 (partner and localizer of BRCA2) (eg, Prior Prior Prior 81308 breast and pancreatic cancer) gene analysis; Authorization Authorization Authorization known familial variant required required required PIK3CA (phosphatidylinositol-4, 5- biphosphate 3-kinase, catalytic subunit Prior Prior Prior 81309 alpha) (eg, colorectal and breast cancer) Authorization Authorization Authorization gene analysis, targeted sequence analysis required required required (eg, exons 7, 9, 20) NPM1 (nucleophosmin) (e.g., acute myeloid Prior Prior Prior 81310 leukemia) gene analysis, exon 12 variants Authorization Authorization Authorization NOT required NOT required NOT required NRAS (neuroblastoma RAS viral [v-ras] oncogene homolog) (eg, colorectal Prior Prior Prior 81311 carcinoma), gene analysis, variants in exon Authorization Authorization Authorization 2 (eg, codons 12 and 13) and exon 3 (eg, NOT required NOT required NOT required codon 61) PABPN1 (poly[A] binding protein nuclear 1) Prior Prior Prior (eg, oculopharyngeal muscular dystrophy) 81312 Authorization Authorization Authorization gene analysis, evaluation to detect abnormal required required required (eg, expanded) alleles PCA3/KLK3 (prostate cancer antigen 3 [non- protein coding]/kallikrein-related peptidase 3 PG0367 Gene Expression Analysis for Prostate 81313 [prostate specific antigen]) ratio (eg, prostate Cancer cancer) PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) (eg, Prior Prior Prior 81314 gastrointestinal stromal tumor [GIST]), gene Authorization Authorization Authorization analysis, targeted sequence analysis (eg, NOT required NOT required NOT required exons 12, 18) PML/RARalpha, (t(15;17)), (promyelocytic leukemia/retinoic acid receptor alpha) (e.g., Prior Prior Prior 81315 promyelocytic leukemia) translocation Authorization Authorization Authorization analysis; common breakpoints (e.g., intron 3 NOT required NOT required NOT required and intron 6), qualitative or quantitative PML/RARalpha, (t(15;17)), (promyelocytic Prior Prior Prior 81316 leukemia/retinoic acid receptor alpha) (e.g., Authorization Authorization Authorization promyelocytic leukemia) translocation NOT required NOT required NOT required

PG0041 – 08/06/2021 analysis; single breakpoint (e.g., intron 3, intron 6 or exon 6), qualitative or quantitative PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81317 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; full sequence analysis PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81318 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; known familial variants PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non- PG0302 Genetic Testing for Lynch Syndrome 81319 polyposis colorectal cancer, Lynch and Polyposis Syndromes syndrome) gene analysis; duplication/deletion variants PLCG2 (phospholipase C gamma 2) (eg, Prior Prior Prior chronic lymphocytic leukemia) gene 81320 Authorization Authorization Authorization analysis, common variants (eg, R665W, NOT required NOT required NOT required S707F, L845F) PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma 81321 PG0336 PTEN Genetic Testing tumor syndrome) gene analysis; full sequence analysis PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma 81322 PG0336 PTEN Genetic Testing tumor syndrome) gene analysis; known familial variant PTEN (phosphatase and tensin homolog) (e.g., Cowden syndrome, PTEN hamartoma 81323 PG0336 PTEN Genetic Testing tumor syndrome) gene analysis; duplication/deletion variant PMP22 (peripheral myelin protein 22) (e.g., Prior Charcot- Marie-Tooth, hereditary neuropathy 81324 Non-Covered Non-Covered Authorization with liability to pressure palsies) gene required analysis; duplication/deletion analysis PMP22 (peripheral myelin protein 22) (e.g., Prior Charcot- Marie-Tooth, hereditary neuropathy 81325 Non-Covered Non-Covered Authorization with liability to pressure palsies) gene required analysis; full sequence analysis PMP22 (peripheral myelin protein 22) (e.g., Prior Charcot- Marie-Tooth, hereditary neuropathy 81326 Non-Covered Non-Covered Authorization with liability to pressure palsies) gene required analysis; known familial variant SEPT9 (Septin9) (eg, colorectal cancer) 81327 PG0065 Colorectal Cancer Screening methylation analysis SLCO1B1 (solute carrier organic anion Prior Prior transporter family, member 1B1) (eg, 81328 Authorization Non-Covered Authorization adverse drug reaction), gene analysis, required required common variant(s) (eg, *5) SMN1(survival of motor neuron 1, telomeric) PG0398 Genetic Testing for Spinal Muscular 81329 (eg, spinal muscular atrophy) gene analysis; Atrophy dosage/deletion analysis (eg, carrier testing),

PG0041 – 08/06/2021 includes SMN2 (survival of motor neuron 2, centromeric) analysis , if performed SMPD1(sphingomyelin phosphodiesterase Prior Prior 1, acid lysosomal) (e.g., Niemann-Pick 81330 Authorization Non-Covered Authorization disease, Type A) gene analysis, common required required variants (e.g., R496L, L302P, fsP330) SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and Prior 81331 ubiquitin protein ligase E3A) (e.g., Prader- Non-Covered Non-Covered Authorization Willi syndrome and/or Angelman syndrome), required methylation analysis SERPINA1 (serpin peptidase inhibitor, clade A, alpha-1 antiproteinase, antitrypsin, Prior Prior Prior 81332 member 1) (e.g., alpha-1-antitrypsin Authorization Authorization Authorization deficiency), gene analysis, common variants required required required (e.g., *S and *Z) TGFBI (transforming growth factor beta- Prior Prior Prior induced) (eg, corneal dystrophy) gene 81333 Authorization Authorization Authorization analysis, common variants (eg, R124H, required required required R124C, R124L, R555W, R555Q) RUNX1 (runt related transcription factor 1) (eg, acute myeloid leukemia, familial platelet Prior Prior Prior 81334 disorder with associated myeloid Authorization Authorization Authorization malignancy), gene analysis, targeted required required required sequence analysis (eg, exons 3-8) TPMT (thiopurine S-methyltransferase) (eg, Prior Prior Prior drug metabolism), gene analysis, common 81335 Authorization Authorization Authorization variants (eg, required required required *2, *3) SMN1(survival of motor neuron 1, telomeric) PG0398 Genetic Testing for Spinal Muscular 81336 (eg, spinal muscular atrophy) gene analysis; Atrophy full gene sequence SMN1(survival of motor neuron 1, telomeric) PG0398 Genetic Testing for Spinal Muscular 81337 (eg, spinal muscular atrophy) gene analysis; Atrophy known familial sequence variant(s) MPL (MPL proto-oncogene , thrombopoietin No Prior No Prior No Prior receptor) (eg, myeloproliferative disorder ) 81338 Authorization Authorization Authorization gene analysis; common variants (eg, required required required W515A, W515K, W515L, W515R) MPL (MPL proto-oncogene , thrombopoietin No Prior No Prior No Prior 81339 receptor) (eg, myeloproliferative disorder ) Authorization Authorization Authorization gene analysis; sequence analysis, exon 10 required required required TRB@ (T cell antigen receptor, beta) (e.g., leukemia and lymphoma), gene Prior Prior Prior rearrangement analysis to detect abnormal 81340 Authorization Authorization Authorization clonal population(s); using amplification NOT required NOT required NOT required methodology (e.g., polymerase chain reaction) TRB@ (T cell antigen receptor, beta) (e.g., leukemia and lymphoma), gene Prior Prior Prior 81341 rearrangement analysis to detect abnormal Authorization Authorization Authorization clonal population(s); using direct probe NOT required NOT required NOT required methodology (e.g., Southern blot)

PG0041 – 08/06/2021 TRG@ (T cell antigen receptor, gamma) Prior Prior Prior (e.g., leukemia and lymphoma), gene 81342 Authorization Authorization Authorization rearrangement analysis, evaluation to detect NOT required NOT required NOT required abnormal clonal population(s) PPP2R2B (protein phosphatase 2 regulatory Prior Prior Prior subunit Bbeta) (eg, spinocerebellar ataxia) 81343 Authorization Authorization Authorization gene analysis, evaluation to detect abnormal required required required (eg, expanded) alleles TBP (TATA box binding protein) (eg, Prior Prior Prior spinocerebellar ataxia) gene analysis, 81344 Authorization Authorization Authorization evaluation to detect abnormal (eg, required required required expanded) alleles TERT (telomerase reverse transcriptase) Prior Prior Prior (eg, thyroid carcinoma, glioblastoma 81345 Authorization Authorization Authorization multiforme) gene analysis, targeted required required required sequence analysis (eg, promoter region) TYMS (thymidylate synthetase) (eg, 5- Prior Prior Prior fluorouracil/5- FU drug metabolism), gene 81346 Authorization Authorization Authorization analysis, common variant(s) (eg,tandem required required required repeat variant) SF3B1 (splicing factor [3b] subunit B1) (eg, No Prior No Prior No Prior myelodysplastic syndrome/acute myeloid 81347 Authorization Authorization Authorization leukemia) gene analysis, common variants required required required (eg, A672T, E622D, L833F, R625C, R625L) SRSF2 (serine and arginine-rich splicing No Prior No Prior No Prior factor 2) (eg, myelodysplastic syndrome, 81348 Authorization Authorization Authorization acute myeloid leukemia) gene analysis, required required required common variants (eg, P95H, P95L) UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide A1) (e.g., irinotecan PG0391 UGT1A1 Targeted Mutation Analysis 81350 metabolism), gene analysis, common for Irinotecan Response variants (e.g., *28, *36, *37) TP53 (tumor protein 53) (eg, Li-Fraumeni Prior Prior Prior 81351 syndrome) gene analysis; full gene Authorization Authorization Authorization sequence required required required TP53 (tumor protein 53) (eg, Li-Fraumeni No Prior No Prior No Prior 81352 syndrome) gene analysis; targeted sequence Authorization Authorization Authorization analysis (eg, 4 oncology) required required required TP53 (tumor protein 53) (eg, Li-Fraumeni Prior Prior Prior 81353 syndrome) gene analysis; known familial Authorization Authorization Authorization variant required required required VKORC1 (vitamin K epoxide reductase complex, subunit 1) (e.g., warfarin 81355 PG0390 Genetic Testing for Warfarin Dose metabolism), gene analysis, common variant(s) (e.g., -1639G>A, c.173+1000C>T) U2AF1 (U2 small nuclear RNA auxiliary factor 1) (eg, myelodysplastic syndrome, No Prior No Prior No Prior 81357 acute myeloid leukemia) gene analysis, Authorization Authorization Authorization common variants (eg, S34F, S34Y, Q157R, required required required Q157P) ZRSR2 (zinc finger CCCH-type, RNA binding motif and serine/arginine-rich 2) (eg, No Prior No Prior No Prior 81360 myelodysplastic syndrome, acute myeloid Authorization Authorization Authorization leukemia) gene analysis, common variant(s) required required required (eg, E65fs, E122fs, R448fs)

PG0041 – 08/06/2021 HBB (hemoglobin, subunit beta) (eg, sickle Prior Prior cell anemia, beta thalassemia 81361 Authorization Non-Covered Authorization hemoglobinopathy); common variant(s) (eg, required required HbS, HbC, HbE) HBB (hemoglobin, subunit beta) (eg, sickle Prior Prior 81362 cell anemia, beta thalassemia Authorization Non-Covered Authorization hemoglobinopathy); known familial variant(s) required required HBB (hemoglobin, subunit beta) (eg, sickle Prior Prior cell anemia, beta thalassemia 81363 Authorization Non-Covered Authorization hemoglobinopathy); duplication/deletion required required variant(s) HBB (hemoglobin, subunit beta) (eg, sickle Prior Prior 81364 cell anemia, beta thalassemia Authorization Non-Covered Authorization hemoglobinopathy); full gene sequence required required HLA Class I and II typing, low resolution Prior Prior Prior 81370 (e.g., antigen equivalents); HLA-A, -B, -C, - Authorization Authorization Authorization DRB1/3/4/5, and -DQB1 NOT required NOT required NOT required HLA Class I and II typing, low resolution Prior Prior Prior 81371 (e.g., antigen equivalents); HLA-A, -B, and - Authorization Authorization Authorization DRB1/3/4/5 (e.g., verification typing) NOT required NOT required NOT required HLA Class I typing, low resolution (e.g., Prior Prior Prior 81372 antigen equivalents); complete (i.e., HLA-A, - Authorization Authorization Authorization B, and -C) NOT required NOT required NOT required HLA Class I typing, low resolution (e.g., Prior Prior Prior 81373 antigen equivalents); one locus (e.g., HLA-A, Authorization Authorization Authorization -B, or -C), each NOT required NOT required NOT required HLA Class I typing, low resolution (e.g., Prior Prior Prior 81374 antigen equivalents); one antigen equivalent Authorization Authorization Authorization (e.g., B*27), each NOT required NOT required NOT required HLA Class II typing, low resolution (e.g., Prior Prior Prior 81375 antigen equivalents); HLA-DRB1/3/4/5 and - Authorization Authorization Authorization DQB1 NOT required NOT required NOT required HLA Class II typing, low resolution (e.g., Prior Prior Prior antigen equivalents); one locus (e.g., HLA- 81376 Authorization Authorization Authorization DRB1/3/4/5, - DQB1, -DQA1, -DPB1, or - NOT required NOT required NOT required DPA1), each HLA Class II typing, low resolution (e.g., Prior Prior Prior 81377 antigen equivalents); one antigen equivalent, Authorization Authorization Authorization each NOT required NOT required NOT required HLA Class I typing, high resolution (i.e., Prior Prior Prior 81378 alleles or allele groups); complete (i.e., HLA- Authorization Authorization Authorization A, -B, and -C) NOT required NOT required NOT required HLA Class I typing, high resolution (i.e., Prior Prior Prior 81379 alleles or allele groups); complete (i.e., HLA- Authorization Authorization Authorization A, -B, and -C) NOT required NOT required NOT required HLA Class I typing, high resolution (i.e., Prior Prior Prior 81380 alleles or allele groups); one locus (e.g., Authorization Authorization Authorization HLA-A, -B, or -C), each NOT required NOT required NOT required HLA Class I typing, high resolution (i.e., PG0437 HLA-B1502 & HLA-B5701 81381 alleles or allele groups); one allele or allele Pharmacogenetic Testing group (e.g., B*57:01P), each HLA Class II typing, high resolution (i.e., Prior Prior Prior alleles or allele groups); one locus (e.g., 81382 Authorization Authorization Authorization HLA-DRB1, -DRB3, - DRB4, -DRB5, -DQB1, NOT required NOT required NOT required -DQA1, -DPB1, or -DPA1),

PG0041 – 08/06/2021 Each HLA Class II typing, high resolution (i.e., Prior Prior Prior 81383 alleles or allele groups); one allele or allele Authorization Authorization Authorization group (e.g., HLA- DQB1*06:02P), each NOT required NOT required NOT required Tier 2 Molecular Pathology Procedures Molecular pathology procedure, Level 1 analysis)(e.g., identification of single Prior Authorization required for all product 81400 germline variant [e.g., SNP] by techniques lines such as restriction enzyme digestion or melt curve analysis) Molecular pathology procedure, Level 2 (e.g., 2-10 SNPs, 1 methylated variant, or 1 somatic variant [typically using Prior Authorization required for all product 81401 nonsequencing target variant analysis], or lines detection of a dynamic mutation disorder/triplet repeat) Molecular pathology procedure, Level 3 (eg, >10 SNPs, 2-10 methylated variants, or 2-10 somatic variants [typically using non- sequencing target variant analysis], Prior Authorization required for all product 81402 immunoglobulin and T-cell receptor gene lines rearrangements, duplication/deletion variants of 1 exon, loss of heterozygosity [LOH], uniparental disomy [UPD]) Molecular pathology procedure, Level 4 (eg, analysis of single exon by DNA sequence analysis, analysis of >10 amplicons using Prior Authorization required for all product 81403 multiplex PCR in 2 or more independent lines reactions, mutation scanning or duplication/deletion variants of 2-5 exons) Molecular pathology procedure, Level 5 (eg, analysis of 2-5 exons by DNA sequence analysis, mutation scanning or Prior Authorization required for all product 81404 duplication/deletion variants of 6-10 exons, lines or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis) Molecular pathology procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis, mutation scanning or Prior Authorization required for all product 81405 duplication/deletion variants of 11-25 exons, lines regionally targeted cytogenomic array analysis) Molecular pathology procedure, Level 7 (e.g., analysis of 11-25 exons by DNA Prior Authorization required for all product 81406 sequence analysis, mutation scanning or lines duplication/deletion variants of 26-50 exons, cytogenomic array analysis for neoplasia) Molecular pathology procedure Level 8 (eg, analysis of 26-50 exons by DNA sequence analysis, mutation scanning or Prior Authorization required for all product 81407 duplication/deletion variants of >50 exons, lines sequence analysis of multiple genes on the one platform)

PG0041 – 08/06/2021 Molecular pathology procedure, Level 9 (e.g., analysis of >50 exons in a single gene by DNA sequence analysis) FBN1 (fibrillin 1) (e.g., Marfan syndrome), full gene sequence NF1 (neurofibromin Prior Authorization required for all product 81408 1) (e.g., neurofibromatosis, type 1), full gene lines sequence RYR1 (ryanodine receptor 1, skeletal) (e.g., malignant hyperthermia), full gene sequence VWF (von Willebrand factor) (e.g., von Willebrand disease types 1 and 3), full gene sequence Unlisted molecular pathology procedure Prior Authorization required for all product 81479 lines Genomic Sequencing Procedures and Other Molecular Multianalyte Assays (MAA) Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity 81410 PG0453 Germline Multi-Gene Panel Testing syndrome); duplication/deletion analysis panel, must include analyses for TGFBR1, TGFBR2, MYH11, and COL3A1 Aortic dysfunction or dilation (eg, Marfan syndrome, Loeys Dietz syndrome, Ehler Danlos syndrome type IV, arterial tortuosity 81411 PG0453 Germline Multi-Gene Panel Testing syndrome); duplication/deletion analysis panel, must include analyses for TGFBR1, TGFBR2, MYH11, and COL3A1 Ashkenazi Jewish associated disorders (eg, Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Tay- PG0453 Germline Multi-Gene Panel 81412 Sachs disease), genomic sequence analysis Testing/PG0442 Carrier Screening for Genetic panel, must include sequencing of at least 9 Diseases genes, including ASPA, BLM, CFTR, FANCC, GBA, HEXA, IKBKAP, MCOLN1, and SMPD1 Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); genomic sequence PG0453 Germline Multi-Gene Panel 81413 analysis panel, must include sequencing of Testing/PG0280 Genetic Testing for Cardiac at least 10 genes, including ANK2, CASQ2, Conditions CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, RYR2, and SCN5A

Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic PG0453 Germline Multi-Gene Panel 81414 ventricular tachycardia); duplication/deletion Testing/PG0280 Genetic Testing for Cardiac gene analysis panel, must include analysis Conditions of at least 2 genes, including KCNH2 and KCNQ1 Exome (eg, unexplained constitutional or PG0453 Germline Multi-Gene Panel 81415 heritable disorder or syndrome); sequence Testing/PG0468 Whole Exome Sequencing analysis (WES) and Whole Genome Sequencing (WGS)

PG0041 – 08/06/2021 Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence PG0453 Germline Multi-Gene Panel 81416 analysis, each comparator exome (eg, Testing/PG0468 Whole Exome Sequencing parents, siblings) (List separately in addition (WES) and Whole Genome Sequencing (WGS) to code for primary procedure) Exome (eg, unexplained constitutional or heritable disorder or syndrome); re- PG0453 Germline Multi-Gene Panel 81417 evaluation of previously obtained exome Testing/PG0468 Whole Exome Sequencing sequence (eg, updated knowledge or (WES) and Whole Genome Sequencing (WGS) unrelated condition/syndrome)

Epilepsy genomic sequence analysis panel, PG0453 Germline Multi-Gene Panel must include analyses for ALDH7A1, Testing/PG0467 Genetic Testing for Epilepsy CACNA1A, CDKL5, CHD2, GABRG2, 81419 GRIN2A, KCNQ2, MECP2, PCDH19, POLG, Prior Prior Prior PRRT2, SCN1A, SCN1B, SCN2A, SCN8A, Authorization Authorization Authorization SLC2A1, SLC9A6, STXBP1, SYNGAP1, required required required TCF4, TPP1, TSC1,TSC2, and ZEB2 effective effective effective 5/1/2021 5/1/2021 5/1/2021 Fetal chromosomal aneuploidy (eg, trisomy PG0453 Germline Multi-Gene Panel 21, monosomy X) genomic sequence Testing/PG0287 Non-Invasive Prenatal 81420 analysis panel, circulating cell-free fetal DNA Screening (NIPS)/Cell-Free DNA Screening for in maternal blood, must include analysis of Fetal Aneuploidy chromosomes 13, 18, and 21 Fetal chromosomal microdeletion(s) genomic PG0453 Germline Multi-Gene Panel sequence analysis (eg. DiGeorge syndrome, Testing/PG0287 Non-Invasive Prenatal 81422 Cri-du- chat syndrome), circulating cell-free Screening (NIPS)/Cell-Free DNA Screening for fetal DNA in maternal blood Fetal Aneuploidy Genome (eg, unexplained constitutional or PG0453 Germline Multi-Gene Panel 81425 heritable disorder or syndrome); sequence Testing/PG0468 Whole Exome Sequencing analysis (WES) and Whole Genome Sequencing (WGS) Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence PG0453 Germline Multi-Gene Panel 81426 analysis, each comparator genome (eg, Testing/PG0468 Whole Exome Sequencing parents, siblings) (List separately in addition (WES) and Whole Genome Sequencing (WGS) to code for primary procedure) Genome (eg, unexplained constitutional or heritable disorder or syndrome); re- PG0453 Germline Multi-Gene Panel 81427 evaluation of previously obtained genome Testing/PG0468 Whole Exome Sequencing sequence (eg, updated knowledge or (WES) and Whole Genome Sequencing (WGS) unrelated condition/syndrome) Hearing loss (eg, nonsyndromic hearing loss, Usher syndrome, Pendred syndrome); genomic sequence analysis panel, must include sequencing of at least 60 genes, 81430 PG0453 Germline Multi-Gene Panel Testing including CDH23, CLRN1, GJB2, GPR98, MTRNR1, MYO7A, MYO15A, PCDH15, OTOF, SLC26A4, TMC1, TMPRSS3, USH1C, USH1G, USH2A, and WFS1 Hearing loss (eg, nonsyndromic hearing loss, Usher syndrome, Pendred syndrome); 81431 duplication/deletion analysis panel, must PG0453 Germline Multi-Gene Panel Testing include copy number analyses for STRC and DFNB1 deletions in GJB2 and GJB6 genes

PG0041 – 08/06/2021 Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial PG0067 Genetic Testing for Breast and Ovarian cancer); genomic sequence analysis panel, 81432 Cancers/PG0453 Germline Multi-Gene Panel must include sequencing of at least 10 Testing genes, always including BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, PALB2, PTEN, STK11, and TP53 Hereditary breast cancer-related disorders (eg, hereditary breast cancer, hereditary PG0067 Genetic Testing for Breast and Ovarian ovarian cancer, hereditary endometrial 81433 Cancers/PG0453 Germline Multi-Gene Panel cancer); duplication/deletion analysis panel, Testing must include analyses for BRCA1, BRCA2, MLH1, MSH2, and STK11 Hereditary retinal disorders (eg, retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy), genomic sequence analysis panel, must include sequencing of 81434 at least 15 genes, including ABCA4, CNGA1, PG0453 Germline Multi-Gene Panel Testing CRB1, EYS, PDE6A, PDE6B, PRPF31, PRPH2, RDH12, RHO, RP1, RP2, RPE65, RPGR, and USH2A Hereditary colon cancer disorders (eg, Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis PG0302 Genetic Testing for Lynch Syndrome polyposis); genomic sequence analysis 81435 and Polyposis Syndromes/PG0453 Germline panel, must include analysis of at least 10 Multi-Gene Panel Testing genes, including APC, BMPR1A, CDH1, MLH1, MSH2, MSH6, MUTYH, PTEN, SMAD4 and STK11 Hereditary colon cancer disorders (eg, Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis PG0302 Genetic Testing for Lynch Syndrome 81436 polyposis); duplication/deletion gene and Polyposis Syndromes/PG0453 Germline analysis panel, must include analysis of at Multi-Gene Panel Testing least 5 genes, including MLH1, MSH2, EPCAM, SMAD4, and STK11 Hereditary neuroendocrine tumor disorders (eg, medullary thyroid carcinoma, parathyroid carcinoma, malignant

pheochromocytoma or paraganglioma; 81437 PG0453 Germline Multi-Gene Panel Testing genomic sequence analysis panel, must

include sequencing of at least 6 genes, including MAX, SDHB, SDHC, SDHD, TMEM127, and VHL Hereditary neuroendocrine tumor disorders (eg, medullary thyroid carcinoma, parathyroid carcinoma, malignant 81438 pheochromocytoma or paraganglioma; PG0453 Germline Multi-Gene Panel Testing duplication/deletion analysis panel, must include analyses for SDHB, SDHC, SDHD, and VHL Hereditary cardiomyopathy (eg, hypertrophic PG0280 Genetic Testing for Cardiac 81439 cardiomyopathy, dilated cardiomyopathy, Conditions/PG0453 Germline Multi-Gene Panel arrhythmogenic right ventricular Testing

PG0041 – 08/06/2021 cardiomyopathy), genomic sequence analysis panel, must include sequencing of at least 5 cardiomyopathy-related genes (eg, DSG2, MYBPC3, MYH7, PKP2, TTN) Nuclear encoded mitochondrial genes (eg, neurologic or myopathic phenotypes), genomic sequence panel, must include analysis of at least 100 genes, including 81440 PG0453 Germline Multi-Gene Panel Testing BCS1L, C10orf2, COQ2, COX10, DGUOK, MPV17, OPA1, PDSS2, POLG, POLG2, RRM2B, SCO1, SCO2, SLC25A4, SUCLA2, SUCLG1, TAZ, TK2, and TYMP Noonan spectrum disorders (eg, Noonan syndrome, cardio-facio-cutaneous syndrome, Costello syndrome, LEOPARD syndrome, Noonan-like syndrome), genomic 81442 sequence analysis panel, must include PG0453 Germline Multi-Gene Panel Testing sequencing of at least 12 genes, including BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, and SOS1 Genetic testing for severe inherited conditions (eg, cystic fibrosis, Ashkenazi Jewish-associated disorders [eg, Bloom syndrome, Canavan disease, Fanconi anemia type C, mucolipidosis type VI, Gaucher disease, Tay-Sachs disease], beta hemoglobinopathies, phenylketonuria, 81443 PG0453 Germline Multi-Gene Panel Testing galactosemia), genomic sequence analysis panel, must include sequencing of at least 15 genes (eg ACADM, ARSA, ASPA, ATP7B, BCKDHA, BCKDHB, BLM, CFTR, DHCR7, FANCC, G6PC, GAA, GALT, GB1, GBE1, HBB, HEXA, IKBKAP, MCOLN1, PAH) Targeted genomic sequence analysis panel, solid organ neoplasm, DNA analysis, and Prior Prior Prior RNA analysis when performed, 5-50 genes Authorization Authorization Authorization (eg, ALK, BRAF, CDKN2A, EGFR, ERBB2, required required required KIT, KRAS, NRAS, MET, PDGFRA, 81445 PG0453 Germline Multi-Gene Panel PDGFRB, PGR, PIK3CA, PTEN, RET), Testing/PG0438 Next Generation Sequencing interrogation for sequence variants and copy (NGS) Tests for Advanced Cancer/PG0298 number variants or rearrangements, if Molecular Markers in Fine Needle performed Aspirates of Thyroid Nodules Hereditary peripheral neuropathies (eg, Charcot- Marie-Tooth, spastic paraplegia), genomic sequence analysis panel, must include sequencing of at least 5 peripheral 81448 PG0453 Germline Multi-Gene Panel Testing neuropathy-related genes (eg, BSCL2, GJB1, MFN2, MPZ, REEP1, SPAST, SPG11, SPTLC1) Targeted genomic sequence analysis panel, PG0453 Germline Multi-Gene Panel 81450 hematolymphoid neoplasm or disorder, DNA Testing/PG0438 Next Generation Sequencing analysis, and RNA analysis when performed, (NGS) Tests for Advanced Cancer

PG0041 – 08/06/2021 5-50 genes (eg, BRAF, CEBPA, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KRAS, KIT, MLL, NRAS, NPM1, NOTCH1), interrogation for sequence variants, and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed Targeted genomic sequence analysis panel, solid organ or hematolymphoid neoplasm, DNA analysis, and RNA analysis when performed, 51 or greater genes (eg, ALK, BRAF, CDKN2A, CEBPA, DNMT3A, EGFR, PG0453 Germline Multi-Gene Panel ERBB2, EZH2, FLT3, IDH1, IDH2, JAK2, 81455 Testing/PG0438 Next Generation Sequencing KIT, KRAS, MLL, NPM1, NRAS, MET, (NGS) Tests for Advanced Cancer NOTCH1, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed Whole mitochondrial genome (eg, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS], myoclonic epilepsy with ragged-red fibers [MERFF], 81460 PG0453 Germline Multi-Gene Panel Testing neuropathy, ataxia, and retinitis pigmentosa [NARP], Leber hereditary optic neuropathy [LHON]), genomic sequence, must include sequence analysis of entire mitochondrial genome with heteroplasmy detection Whole mitochondrial genome large deletion analysis panel (eg, Kearns-Sayre syndrome, 81465 chronic progressive external PG0453 Germline Multi-Gene Panel Testing ophthalmoplegia), including heteroplasmy detection, if performed X-linked intellectual disability (XLID) (eg, syndromic and non-syndromic XLID); genomic sequence analysis panel, must include sequencing of at least 60 genes, 81470 PG0453 Germline Multi-Gene Panel Testing including ARX, ATRX, CDKL5, FGD1, FMR1, HUWE1, IL1RAPL, KDM5C, L1CAM, MECP2, MED12, MID1, OCRL, RPS6KA3, and SLC16A2 X-linked intellectual disability (XLID) (eg, syndromic and non-syndromic XLID); duplication/deletion gene analysis, must include analysis of at least 60 genes, 81471 PG0453 Germline Multi-Gene Panel Testing including ARX, ATRX, CDKL5, FGD1, FMR1, HUWE1, IL1RAPL, KDM5C, L1CAM, MECP2, MED12, MID1, OCRL, RPS6KA3, and SLC16A2 Unlisted molecular pathology procedure Prior Prior Prior 81479 Authorization Authorization Authorization required required required Multianalyte Assays with Algorithmic Analyses (MAAA) Autoimmune (rheumatoid arthritis), analysis 81490 PG0362 Vectra® DA of 12 biomarkers using immunoassays,

PG0041 – 08/06/2021 utilizing serum, prognostic algorithm reported as a disease activity score Coronary artery disease, mRNA, gene expression profiling by real-time RT-PCR of 81493 PG0363 CORUS®CAD 23 genes, utilizing whole peripheral blood, algorithm reported as a risk score Oncology (ovarian), biochemical assays of two proteins (CA-125 and HE-4), utilizing 81500 Non-Covered Non-Covered Non-Covered serum, with menopausal status, algorithm reported as a risk score Oncology (ovarian), biochemical assays of five proteins (CA-125, apolipoprotein A1, 81503 beta-2 microglobulin, transferring, and pre- Non-Covered Non-Covered Non-Covered albumin), utilizing serum, algorithm reported as a risk score Oncology (tissue of origin), microarray gene expression profiling of > 2000 genes, PG0364 Gene Expression Profiling for Cancers 81504 utilizing formalin-fixed paraffin-embedded of Unknown Primary Site tissue, algorithm reported as tissue similarity scores Endocrinology (type 2 diabetes), biochemical assays of seven analytes (glucose, HbA1c, insulin, hs-CRP, 81506 Non-Covered Non-Covered Non-Covered adiponectin, ferritin, interleukin 2-receptor alpha), utilizing serum or plasma, algorithm reporting a risk score Fetal aneuploidy (trisomy 21, 18, and 13) PG0287 Non-Invasive Prenatal Screening DNA sequence analysis of selected regions 81507 (NIPS)/Cell-Free DNA Screening for Fetal using maternal plasma, algorithm reported Aneuploidy as a risk score for each trisomy Fetal congenital abnormalities, biochemical assays of two proteins (PAPP-A, hCG [any 81508 Non-Covered Non-Covered Non-Covered form]), utilizing maternal serum, algorithm reported as a risk score Fetal congenital abnormalities, biochemical assays of three proteins (PAPP-A, hCG [any 81509 Non-Covered Non-Covered Non-Covered form], DIA), utilizing maternal serum, algorithm reported as a risk score Fetal congenital abnormalities, biochemical assays of three analytes (AFP, uE3, hCG 81510 Non-Covered Non-Covered Non-Covered [any form]), utilizing maternal serum, algorithm reported as a risk score) Fetal congenital abnormalities, biochemical assays of four analytes (AFP, uE3, hCG [any form], DIA) utilizing maternal serum, 81511 Non-Covered Non-Covered Non-Covered algorithm reported as a risk score (may include additional results from previous biochemical testing) Fetal congenital abnormalities, biochemical assays of five analytes (AFP, uE3, total 81512 hCG, hyperglycosylated hCG, DIA) utilizing Non-Covered Non-Covered Non-Covered maternal serum, algorithm reported as a risk score

PG0041 – 08/06/2021 Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 11 genes (7 content and 4 housekeeping), utilizing Prior Prior Prior 81518 formalin- fixed paraffin embedded tissue, Authorization Authorization Authorization algorithms reported as percentage risk for required required required metastatic recurrence and likelihood of benefit from extended endocrine therapy Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 21 genes, PG0301 Genetic Expression Assays for Breast 81519 utilizing formalin- fixed paraffin embedded Cancer Prognosis tissue, algorithm reported as recurrence score Oncology (breast), mRNA gene expression profiling by hybrid capture of 58 genes (50 PG0301 Genetic Expression Assays for Breast 81520 content and 8 housekeeping), utilizing Cancer Prognosis formalin-fixed paraffin embedded tissue, algorithm reported as a recurrence risk score Oncology (breast), mRNA, microarray gene expression profiling of 70 content genes and 465 housekeeping genes, utilizing fresh PG0301 Genetic Expression Assays for Breast 81521 frozen or formalin-fixed paraffin embedded Cancer Prognosis tissue, algorithm reported as index related to risk of distant metastasis Oncology (breast), mRNA, gene expression profiling by RT-PRC of 12 genes (8 content Prior Prior Prior 81522 and 4 housekeeping), utilizing formalin-fixed Authorization Authorization Authorization paraffin-embedded tissue, algorithm reported required required required as recurrence risk score Oncology (colon), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (7 PG0357 Gene Expression Profiling for 81525 content and 5 housekeeping), utilizing Colorectal Cancer formalin-fixed paraffin- embedded tissue, algorithm reported as a recurrence score Oncology (colorectal) screening, quantitative real- time target and signal amplification of 10 DNA markers (KRAS mutations, promoter 81528 PG0065 Colorectal Cancer Screening methylation of NDRG4 and BMP3) and fecal hemoglobin, utilizing stool, algorithm reported as a positive or negative result Oncology (cutaneous melanoma), mRNA, gene expression profiling by real-time RT- PG0119 Gene Expression Profiling of PCR of 31 genes (28 content and 3 Melanomas housekeeping), utilizing formalin-fixed 81529 Prior Prior Prior paraffin embedded tissue, algorithm reported Authorization Authorization Authorization as recurrence risk, including likelihood of required as of required as of required as of sentinel lymph node metastasis 4/1/2021 4/1/2021 4/1/2021 Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by PG0122 In Vitro Chemoresistance and 81535 DAPI stain and morphology, predictive Chemosensitivity Assays algorithm reported as a drug response score; first single drug or drug combination Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by PG0122 In Vitro Chemoresistance and 81536 DAPI stain and morphology, predictive Chemosensitivity Assays algorithm reported as a drug response score;

PG0041 – 08/06/2021 each additional single drug or drug combination (List separately in addition to code for primary procedure) Oncology (lung), mass spectrometric 8- protein signature, including amyloid A, 81538 utilizing serum, prognostic and predictive PG0111 VeriStrat® algorithm reported as good versus poor overall survival Oncology (high-grade prostate cancer), biochemical assay of four proteins (Total PSA, Free PSA, Intact PSA and human PG0367 Gene Expression Analysis for Prostate 81539 kallikrein-2 [hK2]), utilizing plasma or serum, Cancer prognostic algorithm reported as a probability score Oncology (tumor of unknown origin), mRNA, gene expression profiling by real-time RT- PCR of 92 genes (87 content and 5 housekeeping) to classify tumor into main PG0364 Gene Expression Profiling for Cancers 81540 cancer type and subtype, utilizing formalin- of Unknown Primary Site fixed paraffin-embedded tissue, algorithm reported as a probability of a predicted main cancer type and subtype Oncology (prostate), mRNA gene expression profiling by real-time RT-PCR of 46 genes (31 content and 15 housekeeping), utilizing PG0367 Gene Expression Analysis for Prostate 81541 formalin- fixed paraffin embedded tissue, Cancer algorithm reported as a disease-specific mortality risk score Oncology (prostate), mRNA, microarray gene expression profiling of 22 content Prior Prior Prior 81542 genes, utilizing formalin-fixed paraffin- Authorization Authorization Authorization embedded tissue, algorithm reported as required required required metastasis risk score Oncology (thyroid), gene expression analysis of 142 genes, utilizing fine needle aspirate, 81545 algorithm reported as a categorical result PG0298 Afirma® Thyroid FNA Analysis (eg, benign or suspicious) End-Dated 12/31/2020. Oncology (thyroid), mRNA, gene expression Prior Prior Prior analysis of 10,196 genes, utilizing fine Authorization Authorization Authorization 81546 needle aspirate, algorithm reported as a NOT required NOT required NOT required categorical result (eg, benign or suspicious) PG0298 Molecular Markers in Fine Needle Aspirates of Thyroid Nodules Oncology (prostate), promoter methylation profiling by real-time PCR of 3 genes (GSTP1, APC, RASSF1), utilizing formalin- PG0367 Gene Expression Analysis for Prostate 81551 fixed paraffin embedded tissue, algorithm Cancer reported as a likelihood of prostate cancer detection on repeat biopsy Oncology (uveal melanoma), MRNA, gene PG0119 Gene Expression Profiling of expression profiling by real-time RT-PRC or Melanomas 15 genes (12 content and 3 housekeeping), 81552 utilizing fine needle aspirate or formalin-fixed Prior Prior Prior paraffin-embedded tissue, algorithm reported Authorization Authorization Authorization as risk of metastasis required required required

PG0041 – 08/06/2021 Pulmonary disease (idiopathic pulmonary fibrosis [IPF]), mRNA, gene expression Non-Covered analysis of 190 genes, utilizing Prior 81554 transbronchial biopsies, diagnostic algorithm Non-Covered Non-Covered Authorization reported as categorical result (eg, positive or required as negative for high probability of usual of 4/1/2021 interstitial pneumonia [UIP]) Cardiology (heart transplant), mRNA, gene expression profiling by real-time quantitative PCR of 20 genes (11 content and 9 PG0340 AlloMap™ Molecular-Expression 81595 housekeeping), utilizing subfraction of Blood Test peripheral blood, algorithm reported as a rejection risk score Infectious disease, chronic hepatitis C virus (HCV) infection, six biochemical assays (ALT, A2-macroglobulin, apolipoprotein A-1, Prior Prior Prior 81596 total bilirubin, GGT, and haptoglobin) utilizing Authorization Authorization Authorization serum, prognostic algorithm reported as required required required scores for fibrosis and necroinflammatory activity in liver Prior Prior Prior Unlisted multianalyte assay with algorithmic 81599 Authorization Authorization Authorization analysis required required required Cytogenetic Studies 88230 Tissue culture for non-neoplastic disorders; PG0375 Molecular Cytogenetic Testing lymphocyte 88233 Tissue culture for non-neoplastic disorders; PG0375 Molecular Cytogenetic Testing skin or other solid tissue biopsy 88235 Tissue culture for non-neoplastic disorders; PG0375 Molecular Cytogenetic Testing amniotic fluid or chorionic villus cells 88237 Tissue culture for neoplastic disorders; bone PG0375 Molecular Cytogenetic Testing marrow, blood cells 88239 Tissue culture for neoplastic disorders; solid PG0375 Molecular Cytogenetic Testing tumor 88240 Cryopreservation, freezing and storage of PG0375 Molecular Cytogenetic Testing cells, each cell line 88241 Thawing and expansion of frozen cells, each PG0375 Molecular Cytogenetic Testing aliquot 88245 Chromosome analysis for breakage syndromes; baseline Sister Chromatid PG0375 Molecular Cytogenetic Testing Exchange (SCE), 20-25 cells 88248 Chromosome analysis for breakage syndromes; baseline breakage, score 50- 100 cells, count 20 cells, 2 karyotypes (eg, PG0375 Molecular Cytogenetic Testing for ataxia telangiectasia, Fanconi anemia, fragile X) 88249 Chromosome analysis for breakage syndromes; score 100 cells, clastogen stress PG0375 Molecular Cytogenetic Testing (eg, diepoxybutane, mitomycin C, ionizing radiation, UV radiation) 88261 Chromosome analysis; count 5 cells, 1 PG0375 Molecular Cytogenetic Testing karyotype, with banding 88262 Chromosome analysis; count 15-20 cells, 2 PG0375 Molecular Cytogenetic Testing karyotypes, with banding

PG0041 – 08/06/2021 88263 Chromosome analysis; count 45 cells for PG0375 Molecular Cytogenetic Testing mosaicism, 2 karyotypes, with banding 88264 Chromosome analysis; analyze 20-25 cells PG0375 Molecular Cytogenetic Testing 88267 Chromosome analysis, amniotic fluid or chorionic villus, count 15 cells, 1 karyotype, PG0375 Molecular Cytogenetic Testing with banding 88269 Chromosome analysis, in situ for amniotic fluid cells, count cells from 6-12 colonies, 1 PG0375 Molecular Cytogenetic Testing karyotype, with banding 88271 Molecular cytogenetics; DNA probe, each PG0375 Molecular Cytogenetic Testing (eg, FISH) 88272 Molecular cytogenetics; chromosomal in situ hybridization, analyze 3-5 cells (eg, for PG0375 Molecular Cytogenetic Testing derivatives and markers) 88273 Molecular cytogenetics; chromosomal in situ hybridization, analyze 10-30 cells (eg, for PG0375 Molecular Cytogenetic Testing microdeletions) 88274 Molecular cytogenetics; interphase in situ PG0375 Molecular Cytogenetic Testing hybridization, analyze 25-99 cells 88275 Molecular cytogenetics; interphase in situ PG0375 Molecular Cytogenetic Testing hybridization, analyze 100-300 cells 88280 Chromosome analysis; additional PG0375 Molecular Cytogenetic Testing karyotypes, each study 88283 Chromosome analysis; additional specialized PG0375 Molecular Cytogenetic Testing banding technique (eg, NOR, C-banding) 88285 Chromosome analysis; additional cells PG0375 Molecular Cytogenetic Testing counted, each study 88289 Chromosome analysis; additional high PG0375 Molecular Cytogenetic Testing resolution study 88291 Cytogenetics and molecular cytogenetics, PG0375 Molecular Cytogenetic Testing interpretation and report 88299 Unlisted cytogenetic study PG0375 Molecular Cytogenetic Testing Proprietary MAA Oncology (hepatic), mRNA expression levels of 161 genes, utilizing fresh hepatocellular 0006M carcinoma tumor tissue, with alpha- Non-Covered Non-Covered Non-Covered fetoprotein level, algorithm reported as a risk classifier Oncology (gastrointestinal neuroendocrine tumors), real-time PCR expression analysis 0007M of 51 genes, utilizing whole peripheral blood, Non-Covered Non-Covered Non-Covered algorithm reported as a nomogram of tumor disease index Oncology, prostate cancer, mRNA expression assay of 12 genes (10 content and 2 housekeeping), RT- hyphenPCR test 0011M Non-Covered Non-Covered Non-Covered utilizing blood plasma and/or urine, algorithms to predict high-hyphengrade prostate cancer risk Oncology (urothelial), mRNA, gene expression profiling by real-hyphentime quantitative PCR of five genes (MDK, 0012M Non-Covered Non-Covered Non-Covered HOXA13, CDC2 [CDK1], IGFBP5, and XCR2), utilizing urine, algorithm reported as a risk score for having urothelial carcinoma

PG0041 – 08/06/2021 Oncology (urothelial), mRNA, gene expression profiling by real-hyphentime quantitative PCR of five genes (MDK, 0013M HOXA13, CDC2 [CDK1], IGFBP5, and Non-Covered Non-Covered Non-Covered CXCR2), utilizing urine, algorithm reported as a risk score for having recurrent urothelial carcinoma Proprietary Laboratory Analyses 0001U Red blood cell antigen typing, DNA, human Prior erythrocyte antigen gene analysis of 35 Authorization Non-Covered antigens from 11 blood groups, utilizing Non-Covered required whole blood, common RBC alleles reported 0005U Oncology (prostate) gene expression profile by real-time RT-PCR of 3 genes (ERG, Non-Covered Non-Covered Non-Covered PCA3, and SPDEF), urine, algorithm reported as risk score 0009U Oncology (breast cancer), ERBB2 (HER2) copy number by FISH, tumor cells from formalin fixed paraffin embedded tissue Non-Covered Non-Covered Non-Covered isolated using image- based dielectrophoresis (DEP) sorting, reported as ERBB2 gene amplified or non-amplified 0012U Germline disorders, gene rearrangement detection by whole genome next-generation Non-Covered Non-Covered Non-Covered sequencing, DNA, whole blood, report of specific gene rearrangement(s) 0013U Oncology (solid organ neoplasia), gene rearrangement detection by whole genome next-generation sequencing, DNA, fresh or Non-Covered Non-Covered Non-Covered frozen tissue or cells, report of specific gene rearrangement(s) 0014U Hematology (hematolymphoid neoplasia), gene rearrangement detection by whole genome next- generation sequencing, DNA, Non-Covered Non-Covered Non-Covered whole blood or bone marrow, report of specific gene rearrangement(s) 0016U Oncology (hematolymphoid neoplasia), RNA, BCR/ABL1 major and minor breakpoint Prior fusion transcripts, quantitative PCR Authorization Non-Covered Non-Covered amplification, blood or bone marrow, report required of fusion not detected or detected with quantitation 0017U Oncology (hematolymphoid neoplasia), JAK2 mutation, DNA, PCR amplification of Prior exons 12-14 and sequence analysis, blood Authorization Non-Covered Non-Covered or bone marrow, report of JAK2 mutation not required detected or detected 0018U Oncology (thyroid), microRNA profiling by RT-PCR of 10 microRNA sequences, Prior utilizing fine needle aspirate, algorithm Non-Covered Authorization Non-Covered reported as a positive or negative result for required moderate to high risk of malignancy 0019U Oncology, RNA, gene expression by whole transcriptome sequencing, formalin-fixed Non-Covered Non-Covered Non-Covered paraffin embedded tissue or fresh frozen

PG0041 – 08/06/2021 tissue, predictive algorithm reported as potential targets for therapeutic agents 0022U Targeted genomic sequence analysis panel, non-small cell lung neoplasia, DNA and RNA Prior Prior analysis, 23 genes, interrogation for Authorization Authorization Non-Covered sequence variants and rearrangements, required required reported as presence/absence of variants and associated therapy(ies) to consider 0023U Oncology (acute myelogenous leukemia), DNA, genotyping of internal tandem duplication, p.D835, p.I836, using Prior mononuclear cells, reported as detection or Authorization Non-Covered Non-Covered non- detection of FLT3 mutation and required indication for or against the use of midostaurin 0026U Oncology (thyroid), DNA and mRNA of 112 genes, next-generation sequencing, fine Prior needle aspirate of thyroid nodule, algorithmic Non-Covered Authorization Non-Covered analysis reported as a categorical result required ("Positive, high probability of malignancy" or "Negative, low probability of malignancy") 0027U JAK2 (Janus kinase 2) (eg, Prior myeloproliferative disorder) gene analysis, Authorization Non-Covered Non-Covered targeted sequence analysis exons 12-15 required 0029U Drug metabolism (adverse drug reactions and drug response), targeted sequence analysis (ie, CYP1A2, CYP2C19, CYP2C9, Non-Covered Non-Covered Non-Covered CYP2D6, CYP3A4, CYP3A5, CYP4F2, SLCO1B1, VKORC1 and rs12777823) 0030U Drug metabolism (warfarin drug response), targeted sequence analysis (ie, CYP2C9, Non-Covered Non-Covered Non-Covered CYP4F2, VKORC1, rs12777823) 0031U CYP1A2 (cytochrome P450 family 1, subfamily A, member 2)(eg, drug Non-Covered Non-Covered Non-Covered metabolism) gene analysis, common variants (ie, *1F, *1K, *6, *7) 0032U COMT (catechol-O-methyltransferase)(drug metabolism) gene analysis, c.472G>A Non-Covered Non-Covered Non-Covered (rs4680) variant 0033U HTR2A (5-hydroxytryptamine receptor 2A), HTR2C (5- hydroxytryptamine receptor 2C) (eg, citalopram metabolism) gene analysis, Non-Covered Non-Covered Non-Covered common variants (ie, HTR2A rs7997012 [c.614-2211T>C], HTR2C rs3813929 [c.- 759C>T] and rs1414334 [c.551-3008C>G]) 0034U TPMT (thiopurine S-methyltransferase), NUDT15 (nudix hydroxylase 15)(eg, thiopurine metabolism), gene analysis, Non-Covered Non-Covered Non-Covered common variants (ie, TPMT *2, *3A, *3B, *3C, *4, *5, *6, *8, *12; NUDT15 *3, *4, *5) 0036U Exome (ie, somatic mutations), paired formalin-fixed paraffin-embedded tumor Non-Covered Non-Covered Non-Covered tissue and normal specimen, sequence analyses

PG0041 – 08/06/2021 0037U Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 Prior Prior genes, interrogation for sequence variants, Authorization Authorization Non-Covered gene copy number amplifications, gene required required rearrangements, microsatellite instability and tumor mutational burden 0040U BCR/ABL1 (t(9;22)) (eg, chronic Prior myelogenous leukemia) translocation Authorization Non-Covered Non-Covered analysis, major breakpoint, quantitative required 0045U Oncology (breast ductal carcinoma in situ), mRNA, gene expression profiling by real- Prior time RT-PCR of 12 genes (7 content and 5 Non-Covered Authorization Non-Covered housekeeping), utilizing formalin-fixed required paraffin-embedded tissue, algorithm reported as recurrence score 0046U FLT3 (fms-related tyrosine kinase 3) (eg, Prior acute myeloid leukemia) internal tandem Authorization Non-Covered Non-Covered duplication (ITD) variants, quantitative required 0047U Oncology (prostate), mRNA, gene Non-Covered expression profiling by real-time RT- PCR of Prior Prior 17 genes (12 content and 5 housekeeping), Non-Covered Authorization Authorization utilizing formalin- fixed paraffin-embedded required required as tissue, algorithm reported as a risk score of 1/1/2021 0048U Oncology (solid organ neoplasia), DNA, targeted sequencing of protein- coding exons of 468 cancer-associated genes, Prior Prior including interrogation for somatic mutations Authorization Authorization Non-Covered and microsatellite instability, matched with required required normal specimens, utilizing formalin-fixed paraffin-embedded tumor tissue, report of clinically significant mutation(s) 0049U NPM1 (nucleophosmin) (eg, acute myeloid Prior leukemia) gene analysis, quantitative Authorization Non-Covered Non-Covered required 0050U Targeted genomic sequence analysis panel, acute myelogenous leukemia, DNA analysis, Prior 194 genes, interrogation for sequence Authorization Non-Covered Non-Covered variants, copy number variants or required rearrangements 0053U Oncology (prostate cancer), FISH analysis of 4 genes (ASAP1, HDAC9, CHD1 and Non-Covered Non-Covered Non-Covered PTEN), needle biopsy specimen, algorithm reported as probability of higher tumor grade 0055U Cardiology (heart transplant), cell-free DNA, PCR assay of 96 DNA target sequences (94 Non-Covered Non-Covered Non-Covered single nucleotide polymorphism targets and two control targets), plasma 0056U Hematology (acute myelogenous leukemia), DNA, whole genome next- generation sequencing to detect gene Non-Covered Non-Covered Non-Covered rearrangement(s), blood or bone marrow, report of specific gene rearrangement(s) 0060U Twin zygosity, genomic targeted sequence analysis of chromosome 2, using circulating Non-Covered Non-Covered Non-Covered cell-free fetal DNA in maternal blood

PG0041 – 08/06/2021 0069U Oncology (colorectal), microRNA, RT-PCR expression profiling of miR-31-3p, Non-Covered Non-Covered Non-Covered formalin-fixed paraffin-embedded tissue, algorithm reported as an expression score 0070U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, common and select rare variants (ie, *2, *3, *4, *4N, *5, Prior Prior *6, *7, *8, *9, *10, *11, *12, *13, *14A, Authorization Authorization Non-Covered *14B, *15, *17, *29, *35, *36, *41, *57, *61, required required *63, *68, CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, full gene sequence 0071U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug Prior Prior metabolism) gene analysis, full gene Authorization Authorization Non-Covered sequence (List separately in addition to required required code for primary procedure) (Use 0071U in conjunction with 0070U) 0072U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted Prior Prior sequence analysis (ie, CYP2D6-2D7 hybrid Authorization Authorization Non-Covered gene) (List separately in addition to code required required for primary procedure) (Use 0072U in conjunction with 0070U) 0073U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted Prior Prior sequence analysis (ie, CYP2D7-2D6 hybrid Authorization Authorization Non-Covered gene) (List separately in addition to code required required for primary procedure) (Use 0073U in conjunction with 0070U) 0074U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted Prior Prior sequence analysis (ie, non-duplicated gene Authorization Authorization Non-Covered when duplication/multiplication is trans) required required (List separately in addition to code for primary procedure) (Use 0074U in conjunction with 0070U) 0075U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted Prior Prior sequence analysis (ie, 5’ gene Authorization Authorization Non-Covered duplication/multiplication) (List separately required required in addition to code for primary procedure) (Use 0075U in conjunction with 0070U) 0076U CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, targeted Prior Prior sequence analysis (ie, 3’ gene Authorization Authorization Non-Covered duplication/multiplication) (List separately required required in addition to code for primary procedure) (Use 0076U in conjunction with 0070U)

PG0041 – 08/06/2021 0078U Pain management (opioid-use disorder) genotyping panel, 16 common variants (ie, ABCB1, COMT, DAT1, DBH, DOR, DRD1, DRD2, DRD4, GABA, GAL, HTR2A, HTTLPR, MTHFR, MUOR, OPRK1, Non-Covered Non-Covered Non-Covered OPRM1), buccal swab or other germline tissue sample, algorithm reported as positive or negative risk of opioid-use disorder 0079U Comparative DNA analysis using multiple selected single-nucleotide polymorphisms Non-Covered Non-Covered Non-Covered (SNPs), urine and buccal DNA, for specimen identity verification 0084U Red blood cell antigen typing, DNA, genotyping of 10 blood groups with Non-Covered Non-Covered Non-Covered phenotype prediction of 37 red blood cell antigens 0087U Cardiology (heart transplant), mRNA gene expression profiling by microarray of 1283 genes, transplant biopsy tissue, allograft Non-Covered Non-Covered Non-Covered rejection and injury algorithm reported as a probability score 0088U Transplantation medicine (kidney allograft rejection), microarray gene expression profiling of 1494 genes, utilizing transplant Non-Covered Non-Covered Non-Covered biopsy tissue, algorithm reported as a probability score for rejection 0089U Oncology (melanoma), gene expression profiling by RTqPCR, PRAME and PG0119 Gene Expression Profiling of LINC00518, superficial collection using Melanomas adhesive patch(es) Prior Non-Covered Authorization Non-Covered required 0090U PG0119 Gene Expression Profiling of Melanomas Oncology (cutaneous melanoma), mRNA

gene expression profiling by RT-PCR of 23 Non-Covered genes (14 content and 9 housekeeping), Prior Prior Prior utilizing formalin-fixed paraffin-embedded Authorization Authorization Authorization tissue, algorithm reported as a categorical required required required as of 4/1/2021 0094U Genome (eg, unexplained constitutional or heritable disorder or syndrome), rapid Non-Covered Non-Covered Non-Covered sequence analysis 0101U Hereditary colon cancer disorders (eg, Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis polyposis), genomic sequence analysis Prior Prior panel utilizing a combination of NGS, Authorization Authorization Non-Covered Sanger, MLPA, and array CGH, with required required MmRNA analytics to resolve variants of unknown significance when indicated (15 genes [sequencing and deletion/duplication],

PG0041 – 08/06/2021 EPCAM an GREM1 [deletion/duplication only]) 0102U hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis panel utilizing a Prior Prior combination of NGS, Sanger, MLPA, and Authorization Authorization Non-Covered array CGH, with MmRNA analytics to resolve required required variants of unknown significance when indicated (17 genes [sequencing and deletion/duplication]) 0103U Hereditary ovarian cancer (eg, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis panel utilizing a combination of NGS, Prior Prior Sanger,,MLPA, and array CGH, with Authorization Authorization Non-Covered MmRNA required required analytics to resolve variants of unknown significance when indicated (24 genes [sequencing and deletion/duplication], EPCAM [deletion/duplication only]) 0111U Oncology (colon cancer), targeted KRAS Prior Prior (codons 12, 13, and 61) and NRAS (codons Authorization Authorization Non-Covered 12, 13, and 61) gene analysis utilizing required required formalin-fixed paraffin-embedded tissue 0118U Transplantation medicine, quantification of donor-derived cell-free DNA using whole genome next-generation sequencing, Non-Covered Non-Covered Non-Covered plasma, reported as percentage of donor- derived cell-free DNA in the total cell-free DNA 0120U Oncology (B-cell lymphoma classification), mRNA, gene expression profiling by fluorescent probe hybridization of 58 genes (45 content and 13 housekeeping genes), formalin-fixe paraffin-embedded tissue, Non-Covered Non-Covered Non-Covered algorithm reported as likelihood for primary mediastinal B-cell lymphoma (PMBCL) and diffuse large B-cell lymphoma (DLBCL) with cell of origin subtyping in the latter 0129U Hereditary breast cancer–related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial Prior Prior cancer), genomic sequence analysis and Authorization Authorization Non-Covered deletion/duplication analysis panel (ATM, required required BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, and TP53) 0130U Hereditary colon cancer disorders (eg, Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis polyposis), targeted mRNA sequence analysis panel (APC, CDH1, Non-Covered Non-Covered Non-Covered CHEK2, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, and TP53) (List separately in addition to code for primary procedure) (Use 0130U in conjunction with 81435, 0101U)

PG0041 – 08/06/2021 0131U Hereditary breast cancer–related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, Non-Covered Non-Covered Non-Covered hereditary endometrial cancer), targeted mRNA sequence analysis panel (13 genes) 0132U Hereditary ovarian cancer–related disorders (eg, hereditary breast cancer, hereditary ovarian cancer, Non-Covered Non-Covered Non-Covered hereditary endometrial cancer), targeted mRNA sequence analysis panel (17 genes) 0133U Hereditary prostate cancer–related disorders, targeted mRNA sequence Non-Covered Non-Covered Non-Covered analysis panel (11 genes) 0134U Hereditary pan cancer (eg, hereditary breast and ovarian cancer, hereditary endometrial cancer, Non-Covered Non-Covered Non-Covered hereditary colorectal cancer), targeted mRNA sequence analysis panel (18 genes) 0135U Hereditary gynecological cancer (eg, hereditary breast and ovarian cancer, hereditary endometrial Non-Covered Non-Covered Non-Covered cancer, hereditary colorectal cancer), targeted mRNA sequence analysis panel (12 genes) 0136U ATM (ataxia telangiectasia mutated) (eg, ataxia Non-Covered Non-Covered Non-Covered telangiectasia) mRNA sequence analysis 0137U PALB2 (partner and localizer of BRCA2) (eg, breast Non-Covered Non-Covered Non-Covered and pancreatic cancer) mRNA sequence analysis 0138U BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (eg, Non-Covered Non-Covered Non-Covered hereditary breast and ovarian cancer) mRNA sequence analysis 0153U Oncology (breast), mRNA, gene expression profiling by next-generation sequencing of 101 genes, utilizing formalin- fixed paraffin-embedded tissue, Non-Covered Non-Covered Non-Covered algorithm reported as a triple negative breast cancer clinical subtype(s) with information on immune cell involvement 0154U Oncology (urothelial cancer), RNA, Prior analysis by real-time RT-PCR of the Authorization Non-Covered Non-Covered FGFR3 (fibroblast growth factor receptor 3) required gene analysis (ie, p.R248C [c.742C>T],

PG0041 – 08/06/2021 p.S249C [c.746C>G], p.G370C [c.1108G>T], p.Y373C [c.1118A>G], FGFR3-TACC3v1, and FGFR3-TACC3v3)

0155U Oncology (breast cancer), DNA, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha) (eg, breast Prior Prior cancer) gene analysis (ie, p.C420R, Authorization Authorization Non-Covered p.E542K, p.E545A, p.E545D [g.1635G>T required required only], p.E545G, p.E545K, p.Q546E, p.Q546R, p.H1047L, p.H1047R,

0156U Copy number (eg, intellectual disability, Non-Covered Non-Covered Non-Covered dysmorphology), sequence analysis 0157U APC (APC regulator of WNT signaling pathway) (eg, familial adenomatosis Non-Covered Non-Covered Non-Covered polyposis [FAP]) mRNA sequence analysis 0158U MLH1 (mutL homolog 1) (eg, hereditary non- polyposis colorectal cancer, Lynch syndrome) mRNA sequence analysis (List Non-Covered Non-Covered Non-Covered separately in addition to code for primary procedure) 0159U MSH2 (mutS homolog 2) (eg, hereditary colon cancer, Lynch syndrome) mRNA Non-Covered Non-Covered Non-Covered sequence analysis (List separately in addition to code for primary procedure) 0160U MSH6 (mutS homolog 6) (eg, hereditary colon cancer, Lynch syndrome) mRNA Non-Covered Non-Covered Non-Covered sequence analysis (List separately in addition to code for primary procedure 0161U PMS2 (PMS1 homolog 2, mismatch repair system component) (eg, hereditary nonpolyposis colorectal cancer, Lynch Non-Covered Non-Covered Non-Covered syndrome) mRNA sequence analysis (List separately in addition to code for primary procedure) 0162U Hereditary colon cancer (Lynch syndrome), targeted mRNA sequence analysis panel (MLH1, MSH2, MSH6, PMS2) (List Non-Covered Non-Covered Non-Covered separately in addition to code for primary procedure) 0168U Fetal aneuploidy (trisomy 21, 18, and 13) DNA sequence analysis of selected regions using maternal plasma without fetal fraction Non-Covered Non-Covered Non-Covered cutoff, algorithm reported as a risk score for each trisomy 0169U NUDT15 (nudix hydrolase 15) and TPMT (thiopurine S-methyltransferase) (eg, drug Non-Covered Non-Covered Non-Covered metabolism) gene analysis, common variants 0170U Neurology (autism spectrum disorder [ASD]), RNA, next-generation sequencing, saliva, Non-Covered Non-Covered Non-Covered algorithmic analysis, and results reported as predictive probability of ASD diagnosis

PG0041 – 08/06/2021 0171U Targeted genomic sequence analysis panel, acute myeloid leukemia, Prior Prior myelodysplastic syndrome, and Authorization Authorization Non-Covered myeloproliferative neoplasms, DNA required required analysis, 23 genes, interrogation for sequence variants, rearrangements and 0172U Oncology (solid tumor as indicated by the label), somatic mutation analysis of BRCA1 Non-Covered (BRCA1, DNA repair associated), BRCA2 Prior Prior Prior (BRCA2, DNA repair associated) and Authorization Authorization Authorization analysis of homologous recombination required required required as deficiency pathways, DNA, formalin-fixed of 4/1/2021 paraffin-embedded tissue, algorithm quantifying tumor genomic instability score 0173U Psychiatry (ie, depression, anxiety), genomic analysis panel, includes variant Non-Covered Non-Covered Non-Covered analysis of 14 genes 0174U Oncology (solid tumor), mass spectrometric 30 protein targets, formalin-fixed paraffin- embedded tissue, prognostic and predictive algorithm reported as likely, Non-Covered Non-Covered Non-Covered unlikely, or uncertain benefit of 39 chemotherapy and targeted therapeutic oncology agents 0175U Psychiatry (eg, depression, anxiety), genomic analysis panel, variant analysis of Non-Covered Non-Covered Non-Covered 15 genes 0177U Oncology (breast cancer), DNA, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3- kinase catalytic subunit alpha) gene Non-Covered Non-Covered Non-Covered analysis of 11 gene variants utilizing plasma, reported as PIK3CA gene mutation status 0179U Oncology (non-small cell lung cancer), cell- free DNA, targeted sequence analysis of 23 genes (single nucleotide variations, insertions and deletions, fusions without Non-Covered Non-Covered Non-Covered prior knowledge of partner/breakpoint, copy number variations), with report of significant mutation(s) 0180U Red cell antigen (ABO blood group) genotyping (ABO), gene analysis Sanger/chain termination/conventional sequencing, ABO (ABO, alpha 1-3-N- Non-Covered Non-Covered Non-Covered acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) gene, including subtyping, 7 exons 0181U Red cell antigen (Colton blood group) genotyping (CO), gene analysis, AQP1 Non-Covered Non-Covered Non-Covered (aquaporin 1 [Colton blood group]) exon 1 0182U Red cell antigen (Cromer blood group) genotyping (CROM), gene analysis, CD55 Non-Covered Non-Covered Non-Covered (CD55 molecule [Cromer blood group]) exons 1-10

PG0041 – 08/06/2021 0183U Red cell antigen (Diego blood group) genotyping (DI), gene analysis, SLC4A1 Non-Covered Non-Covered Non-Covered (solute carrier family 4 member 1 [Diego blood group]) exon 19 0184U Red cell antigen (Dombrock blood group) genotyping (DO), gene analysis, ART4 Non-Covered Non-Covered Non-Covered (ADP-ribosyltransferase 4 [Dombrock blood group]) exon 2 0185U Red cell antigen (H blood group) genotyping (FUT1), gene analysis, FUT1 Non-Covered Non-Covered Non-Covered (fucosyltransferase 1 [H blood group]) exon 4 0186U Red cell antigen (H blood group) genotyping (FUT2), gene analysis, FUT2 Non-Covered Non-Covered Non-Covered (fucosyltransferase 2) exon 2 0187U Red cell antigen (Duffy blood group) genotyping (FY), gene analysis, ACKR1 Non-Covered Non-Covered Non-Covered (atypical chemokine receptor 1 [Duffy blood group]) exons 1-2 0188U Red cell antigen (Gerbich blood group) genotyping (GE), gene analysis, GYPC Non-Covered Non-Covered Non-Covered (glycophorin C [Gerbich blood group]) exons 1-4 0189U Red cell antigen (MNS blood group) genotyping (GYPA), gene analysis, GYPA Non-Covered Non-Covered Non-Covered (glycophorin A [MNS blood group]) introns 1, 5, exon 2 0190U Red cell antigen (MNS blood group) genotyping (GYPB), gene analysis, GYPB Non-Covered Non-Covered Non-Covered (glycophorin B [MNS blood group]) introns 1, 5, pseudoexon 3 0191U Red cell antigen (Indian blood group) genotyping (IN), gene analysis, CD44 Non-Covered Non-Covered Non-Covered (CD44 molecule [Indian blood group]) exons 2, 3, 6 0192U Red cell antigen (Kidd blood group) genotyping (JK), gene analysis, SLC14A1 Non-Covered Non-Covered Non-Covered (solute carrier family 14 member 1 [Kidd blood group]) gene promoter, exon 9 0193U Red cell antigen (JR blood group) genotyping (JR), gene analysis, ABCG2 Non-Covered Non-Covered Non-Covered (ATP binding cassette subfamily G member 2 [Junior blood group]) exons 2-26 0194U Red cell antigen (Kell blood group) genotyping (KEL), gene analysis, KEL (Kell Non-Covered Non-Covered Non-Covered metallo-endopeptidase [Kell blood group]) exon 8 0195U KLF1 (Kruppel-like factor 1), targeted Non-Covered Non-Covered Non-Covered sequencing (ie, exon 13) 0196U Red cell antigen (Lutheran blood group) genotyping (LU), gene analysis, BCAM Non-Covered Non-Covered Non-Covered (basal cell adhesion molecule [Lutheran blood group]) exon 3 0197U Red cell antigen (Landsteiner-Wiener blood Non-Covered Non-Covered Non-Covered group) genotyping (LW), gene analysis,

PG0041 – 08/06/2021 ICAM4 (intercellular adhesion molecule 4 [Landsteiner-Wiener blood group]) exon 1 0198U Red cell antigen (RH blood group) genotyping (RHD and RHCE), gene analysis Sanger/chain termination/conventional sequencing, RHD Non-Covered Non-Covered Non-Covered (Rh blood group D antigen) exons 1-10 and RHCE (Rh blood group CcEe antigens) exon 5 0199U Red cell antigen (Scianna blood group) genotyping (SC), gene analysis, ERMAP Non-Covered Non-Covered Non-Covered (erythroblast membrane associated protein [Scianna blood group]) exons 4, 12 0200U Red cell antigen (Kx blood group) genotyping (XK), gene analysis, XK (X- Non-Covered Non-Covered Non-Covered linked Kx blood group) exons 1-3 0201U Red cell antigen (Yt blood group) genotyping (YT), gene analysis, ACHE Non-Covered Non-Covered Non-Covered (acetylcholinesterase [Cartwright blood group]) exon 2 0203U Autoimmune (inflammatory bowel disease), mRNA, gene expression profiling by quantitative RT-PCR, 17 genes (15 target and 2 reference genes), whole blood, Non-Covered Non-Covered Non-Covered reported as a continuous risk score and classification of inflammatory bowel disease aggressiveness 0204U Oncology (thyroid), mRNA, gene expression analysis of 593 genes (including BRAF, RAS, RET, PAX8, and NTRK) for sequence variants and Non-Covered Non-Covered Non-Covered rearrangements, utilizing fine needle aspirate, reported as detected or not detected 0205U Ophthalmology (age-related macular degeneration), analysis of 3 gene variants (2 CFH gene, 1 ARMS2 gene), using PCR and MALDI-TOF, buccal swab, reported as Non-Covered Non-Covered Non-Covered positive or negative for neovascular age- related macular-degeneration risk associated with zinc supplements 0208U Oncology (medullary thyroid carcinoma), mRNA, gene expression analysis of 108 Prior Prior genes, utilizing fine needle aspirate, Authorization Authorization Non-Covered algorithm reported as positive or negative required required for medullary thyroid carcinoma 0209U Cytogenomic constitutional (genome-wide) analysis, interrogation of genomic regions for copy number, structural changes and Non-Covered Non-Covered Non-Covered areas of homozygosity for chromosomal abnormalities 0211U Oncology (pan-tumor), DNA and RNA by next-generation sequencing, utilizing Non-Covered Non-Covered Non-Covered formalin-fixed paraffin-embedded tissue, interpretative report for single nucleotide

PG0041 – 08/06/2021 variants, copy number alterations, tumor mutational burden, and microsatellite instability, with therapy association 0212U Rare diseases (constitutional/heritable disorders), whole genome and mitochondrial DNA sequence analysis, including small sequence changes, deletions, duplications, short tandem Non-Covered Non-Covered Non-Covered repeat gene expansions, and variants in non-uniquely mappable regions, blood or saliva, identification and categorization of genetic variants, proband 0213U Rare diseases (constitutional/heritable disorders), whole genome and mitochondrial DNA sequence analysis, including small sequence changes, deletions, duplications, short tandem Non-Covered Non-Covered Non-Covered repeat gene expansions, and variants in non-uniquely mappable regions, blood or saliva, identification and categorization of genetic variants, each comparator genome (eg, parent, sibling) 0214U Rare diseases (constitutional/heritable disorders), whole exome and mitochondrial DNA sequence analysis, including small sequence changes, deletions, duplications, Non-Covered Non-Covered Non-Covered short tandem repeat gene expansions, and variants in non-uniquely mappable regions, blood or saliva, identification and categorization of genetic variants, proband 0215U Rare diseases (constitutional/heritable disorders), whole exome and mitochondrial DNA sequence analysis, including small sequence changes, deletions, duplications, short tandem repeat gene expansions, and Non-Covered Non-Covered Non-Covered variants in non-uniquely mappable regions, blood or saliva, identification and categorization of genetic variants, each comparator exome (eg, parent, sibling) 0216U Neurology (inherited ataxias), genomic DNA sequence analysis of 12 common genes including small sequence changes, deletions, duplications, short tandem Non-Covered Non-Covered Non-Covered repeat gene expansions, and variants in non-uniquely mappable regions, blood or saliva, identification and categorization of genetic variants 0217U Neurology (inherited ataxias), genomic DNA sequence analysis of 51 genes including small sequence changes, deletions, duplications, short tandem Non-Covered Non-Covered Non-Covered repeat gene expansions, and variants in non-uniquely mappable regions, blood or saliva, identification and categorization of genetic variants

PG0041 – 08/06/2021 0218U Neurology (muscular dystrophy), DMD gene sequence analysis, including small sequence changes, deletions, duplications, Non-Covered Non-Covered Non-Covered and variants in non-uniquely mappable regions, blood or saliva, identification and characterization of genetic variants 0220U Oncology (breast cancer), image analysis with artificial intelligence assessment of 12 Non-Covered Non-Covered Non-Covered histologic and immunohistochemical features, reported as a recurrence score 0221U Red cell antigen (ABO blood group) genotyping (ABO), gene analysis, next- generation sequencing, ABO (ABO, alpha Non-Covered Non-Covered Non-Covered 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) gene 0222U Red cell antigen (RH blood group) genotyping (RHD and RHCE), gene analysis, next-generation sequencing, RH Non-Covered Non-Covered Non-Covered proximal promoter, exons 1-10, portions of introns 2-3 0229U BCAT1 (Branched chain amino acid transaminase 1) or IKZF1 (IKAROS family Non-Covered Non-Covered Non-Covered zinc finger 1) (eg, colorectal cancer) promoter methylation analysis 0230U AR (androgen receptor) (eg, spinal and bulbar muscular atrophy, Kennedy disease, X chromosome inactivation), full sequence analysis, including small sequence changes in exonic and intronic regions, Non-Covered Non-Covered Non-Covered deletions, duplications, short tandem repeat (STR) expansions, mobile element insertions, and variants in non-uniquely mappable regions 0231U CACNA1A (calcium voltage-gated channel subunit alpha 1A) (eg, spinocerebellar ataxia), full gene analysis, including small sequence changes in exonic and intronic Non-Covered Non-Covered Non-Covered regions, deletions, duplications, short tandem repeat (STR) gene expansions, mobile element insertions, and variants in non-uniquely mappable regions 0232U CSTB (cystatin B) (eg, progressive myoclonic epilepsy type 1A, Unverricht- Lundborg disease), full gene analysis, including small sequence changes in Non-Covered Non-Covered Non-Covered exonic and intronic regions, deletions, duplications, short tandem repeat (STR) expansions, mobile element insertions, and variants in non-uniquely mappable regions 0233U FXN (frataxin) (eg, Friedreich ataxia), gene analysis, including small sequence changes in exonic and intronic regions, deletions, duplications, short tandem Non-Covered Non-Covered Non-Covered repeat (STR) expansions, mobile element insertions, and variants in non-uniquely mappable regions

PG0041 – 08/06/2021 0234U MECP2 (methyl CpG binding protein 2) (eg, Rett syndrome), full gene analysis, including small sequence changes in exonic and intronic regions, deletions, Non-Covered Non-Covered Non-Covered duplications, mobile element insertions, and variants in non-uniquely mappable regions 0235U PTEN (phosphatase and tensin homolog) (eg, Cowden syndrome, PTEN hamartoma tumor syndrome), full gene analysis, including small sequence changes in Non-Covered Non-Covered Non-Covered exonic and intronic regions, deletions, duplications, mobile element insertions, and variants in non-uniquely mappable regions 0236U SMN1 (survival of motor neuron 1, telomeric) and SMN2 (survival of motor neuron 2, centromeric) (eg, spinal muscular atrophy) full gene analysis, including small Non-Covered Non-Covered Non-Covered sequence changes in exonic and intronic regions, duplications and deletions, and mobile element insertions 0237U Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia), genomic sequence analysis panel including ANK2, CASQ2, CAV3, KCNE1, KCNE2, KCNH2, Non-Covered Non-Covered Non-Covered KCNJ2, KCNQ1, RYR2, and SCN5A, including small sequence changes in exonic and intronic regions, deletions, duplications, mobile element insertions, and variants in non-uniquely mappable regions 0238U Oncology (Lynch syndrome), genomic DNA sequence analysis of MLH1, MSH2, MSH6, PMS2, and EPCAM, including small sequence changes in exonic and intronic Non-Covered Non-Covered Non-Covered regions, deletions, duplications, mobile element insertions, and variants in non- uniquely mappable regions 0239U Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free DNA, analysis of 311 or more genes, interrogation for sequence variants, Non-Covered Non-Covered Non-Covered including substitutions, insertions, deletions, select rearrangements, and copy number variations 0245U Oncology (thyroid), mutation analysis of 10 genes and 37 RNA fusions and expression of 4 mRNA markers using nextgeneration sequencing, fine needle aspirate, report Non-Covered Non-Covered Non-Covered includes associated risk of malignancy expressed as a percentage New Code Effective 04/01/2021 HCPCS CODES

PG0041 – 08/06/2021 G0452 Molecular pathology procedure; physician Prior Prior Prior interpretation and report Authorization Authorization Authorization required required required G9143 Warfarin responsiveness testing by genetic technique using any method, any number of Non-Covered Non-Covered Non-Covered specimen(s) S3800 Genetic testing for amyotrophic lateral Non-Covered Non-Covered Non-Covered sclerosis (ALS) S3840 DNA analysis for germline mutations of the RET proto-oncogene for susceptibility to Non-Covered Non-Covered Non-Covered multiple endocrine neoplasia type 2 S3841 Genetic testing for retinoblastoma Non-Covered Non-Covered Non-Covered S3842 Genetic testing for von Hippel-Lindau Non-Covered Non-Covered Non-Covered disease S3844 DNA analysis of the connexin 26 gene (GJB2) for susceptibility to congenital, Non-Covered Non-Covered Non-Covered profound deafness S3845 Genetic testing for alpha-thalassemia Non-Covered Non-Covered Non-Covered S3846 Genetic testing for hemoglobin E beta- Non-Covered Non-Covered Non-Covered thalassemia S3849 Genetic testing for Niemann-Pick diseases Non-Covered Non-Covered Non-Covered S3850 Genetic testing for sickle cell anemia Non-Covered Non-Covered Non-Covered S3852 DNA analysis for APOE epsilon 4 allele for Non-Covered Non-Covered Non-Covered susceptibility to Alzheimer's disease S3853 Genetic testing for myotonic muscular Non-Covered Non-Covered Non-Covered dystrophy S3854 PG0301 Genetic Expression Assays for Breast Gene expression profiling panel for use in Cancer Prognosis the management of breast cancer treatment S3861 Genetic testing, sodium channel, voltage- gated, type V, alpha subunit (SCN5A) and PG0280 Genetic Testing for Cardiac Conditions variants for suspected Brugada Syndrome S3865 Comprehensive gene sequence analysis for PG0280 Genetic Testing for Cardiac Conditions hypertrophic cardiomyopathy S3866 Genetic analysis for a specific gene mutation for hypertrophic cardiomyopathy (HCM) in an PG0280 Genetic Testing for Cardiac Conditions individual with a known HCM mutation in the family S3870 Comparative genomic hybridization (CGH) PG0296 Comparative Genomic Hybridization microarray testing for developmental delay, (CGH)/Chromosomal Microarray Analysis autism spectrum disorder and/or mental (CMA) retardation

Paramount reserves the right to review and revise our policies periodically when necessary. When there is an update, we will publish the most current policy to https://www.paramounthealthcare.com/services/providers/medical-policies/ .

REVISION HISTORY EXPLANATION ORIGINAL EFFECTIVE DATE: 01/01/2012 Date Explanation & Changes 01/01/13  Updated  Per Medical Director Review, genetic subcommittee, the following genetic codes will not 07/08/13 require a prior authorization; 81206-81208, 81210, 81220-81223, 81240-81245,

PG0041 – 08/06/2021 81250-81251, 81255-81256, 81261-81268, 81270, 81275, 81291, 81310, 81315-81316, 81340-81342, 81350, 81355, 81378-81383.  Per 2014 new code review, updated the configuration code sets to include procedures 12/31/13 G0452 and 81287 to require prior authorization, and procedures 81504 and 81507 to be denied as non-covered.  Added codes 81161, 84999, 85999, 86849, 87999, 88199, 88299, 88380, 88381, 88399, 89398  Removed code S3870 05/13/14  Changed title of medical policy from Genetic and Experimental Laboratory Services to Genetic Testing  Policy reviewed and updated to reflect most current clinical evidence per Medical Policy Steering Committee  Added reference to PG0296 Comparative Genomic Hybridization (CGH) for codes 81228 & 01/13/15 81229 per Medical Policy Steering Committee  Added code effective 1/1/15: 81246, 81288, 81313, 81410, 81411, 81415-81417, 81420, 81425-81427, 81430, 81431, 81435, 81436, 81440, 81445, 81450, 81455, 81460, 81465, 81470, 81471, 81519 06/09/15  Updated descriptions for revised codes effective 1/1/15: 81402-81405  Policy reviewed and updated to reflect most current clinical evidence per Medical Policy Steering Committee  For multianalyte assay with algorithmic analyses code 81519 refer to PG0301 Genetic 10/26/15 Expression Assays for Breast Cancer Prognosis for coverage determination  Added effective 1/1/16 o new codes 81162, 81432, 81433, 81434 that require prior authorization; o 81170, 81218, 81219, 81272, 81273, 81276, 81311, 81314, 81412, 81437, 81438, 81442, 81528, 81545, 81595 that do not require prior authorization; and o 81490, 81493, 81525, 81535, 81536, 81538, 81540 that are non-covered.  Updated effective 1/1/16 revised codes 81210, 81275, 81355, 81435, 81436, 81445, 02/26/16 81450, & 81455.  Added codes 88230-88299, and 0001M-0010M.  Code 88271 has a limit of 25 units per 365 days.  Removed codes 88380 & 88381.  Policy reviewed and updated to reflect most current clinical evidence per The Technology Assessment Working Group (TAWG).  Coverage changes made per CMS guidelines:  Non-covered for all product lines - 81161, 81507, 0009M;  Non-covered for HMO, PPO, Individual Marketplace, Elite and covered with prior authorization for Advantage - 81200. 81205, 81209, 81224, 81252, 81253, 81254, 81257, 81260, 81290, 81324, 81325, 81326, 81330, 81331, 81410, 81411, 81412, 81415, 81416, 81417, 81425, 81426, 81427, 81430, 81431, 81433, 81434, 81438, 81440, 81442, 81460, 03/25/16 81465, 81470, 81471;  Covered with prior authorization for HMO, PPO, Individual Marketplace, Elite and Non- covered for Advantage - 81490, 81504, 81525, 81540;  Covered with prior authorization for Elite and Non- covered for HMO, PPO, Individual Marketplace, Advantage – 81493.  Policy reviewed and updated to reflect most current clinical evidence per TAWG  Codes 81242, 81251, 81302, 81303, 81304 are covered with prior authorization for HMO, PPO, Individual Marketplace, & Advantage and are non-covered for Elite per CMS guidelines.  Added specific non- covered genes/gene components determination for 81400-81408, & 04/22/16 81479 per CMS guidelines as non-covered for all product lines.  Added myRisk test (81479) as non-covered for all product lines per CMS guidelines.  Added reference to new policies: o PG0355 Genetic Testing for Hereditary Thrombophilia (81240, 81241, 81291),

PG0041 – 08/06/2021 o PG0357 Gene Expression Profiling for Colorectal Cancer (81525), PG0360 Genetic Testing for FMR1 Mutations Including Fragile X Syndrome (81243, 81244), PG0363 CORUS® CAD (81493), o PG0364 Cancer Type ID (81540), & o PG0368 GeneSight® Assay for Refractory Depression (81479).  Policy reviewed and updated to reflect most current clinical evidence per TAWG  Policy updated per TAWG determination for PG0298 Afirma® Thyroid FNA Analysis, 6/24/16 PG0334 ThyroSeq® v.2 Next Generation Sequencing, and PG0367 Gene Expression Analysis for Prostate Cancer  CPT code 81224 is now covered without prior authorization for HMO, PPO, Individual 10/28/16 Marketplace, & Elite, in addition, to Advantage.  Policy reviewed and updated to reflect most current clinical evidence per TAWG  Added effective 01/01/17 new CPT code 81327 per PG0065 Colorectal Cancer Screening.  Added effective 01/01/17 new CPT codes 81413, 81414, 81439 per PG0280 Genetic Testing for Cardiac Conditions.  Added effective 01/01/17 new CPT code 81422 per PG0287 Cell-Free DNA Tests For Fetal Aneuploidy.  Added CPT code S3854 per PG0301 Genetic Expression Assays for Breast Cancer Prognosis.  Added CPT codes S3861- S3866 per PG0280 Genetic Testing for Cardiac Conditions.  Added CPT code S3870 per PG0296 Comparative Genomic Hybridization (CGH). 03/24/17  Added effective 01/01/17 new CPT codes 81539 as requires prior authorization for Advantage & non-covered for HMO, PPO, Individual Marketplace, & Elite.  Added CPT codes S3800-S3853 as non- covered for all product lines.  Deleted effective 12/31/16 CPT code 0010M (replaced by 81539).  Deleted effective 12/31/16 CPT codes 81280-81282 per PG0280 Genetic Testing for Cardiac Conditions.  Effective 01/01/17 code 81595 is now non-covered for Advantage per ODM guidelines (continues to be covered without prior authorization for HMO, PPO, Individual Marketplace, & Elite) for PG0340 AlloMap™ Molecular-Expression Blood Test.  Policy reviewed and updated to reflect most current clinical evidence per The Technology Assessment Working Group (TAWG).  Added effective 01/01/18 new CPT codes 81520 & 81521 per PG0301 Genetic Expression Assays for Breast Cancer Prognosis.  Added effective 01/01/18 new CPT codes 81541 & 81551 per PG0367 Gene Expression Analysis for Prostate Cancer.  Effective 12/31/17 deleted code 0008M (replaced by 81520) per PG0301 Genetic Expression Assays for Breast Cancer Prognosis.  Added Proprietary Laboratory Analyses (PLA) Codes 0001U- 0034U per PG0417 Proprietary Laboratory Analyses (PLA) Codes & PG0367 Gene Expression Analysis for Prostate Cancer.  Revised effective 01/01/18 codes 81257, 81432, & 81439. 01/25/18  Added effective 01/01/18 new codes 81105, 81106, 81107, 81108, 81109, 81110, 81111, 81112, 81120, 81121, 81175, 81176, 81238, 81247, 81248, 81249, 81283, 81334, 81335, 81346, 81448 as covered with prior authorization for all product lines per CMS & ODM guidelines.  Added effective 01/01/18 new codes 81230, 81231, 81232 as covered with prior authorization for Advantage per ODM guidelines and non-covered for HMO, PPO, Individual Marketplace, & Elite per CMS guidelines.  Added effective 01/01/18 new codes 81258, 81259, 81269, 81328, 81361, 81362, 81363, 81364 as covered with prior authorization for HMO, PPO, Individual Marketplace, & Advantage and non-covered for Elite per CMS guidelines.  Added code G9143 per PG0390 Genetic Testing for Warfarin Dose.

PG0041 – 08/06/2021  Refer to PG0390 Genetic Testing for Warfarin Dose for coverage determination of codes G9143, 81227 & 81355.  Refer to PG0367 Gene Expression Analysis for Prostate Cancer for coverage determination of codes 81313 & 81539.  Refer to PG0375 Molecular Cytogenetic Testing for coverage determination of code 88271.  Refer to PG0411 Genetic Testing for Duchenne and Becker Muscular Dystrophy for coverage determination of codes 81161 & 81408.  Codes 81432, 81435, 81436, 81445, 81455 removed from PG0336 PTEN Hamartoma Tumor Syndrome.  Policy reviewed and updated to reflect most current clinical evidence per The Technology Assessment Working Group (TAWG).  Added reference to these genetic policies: o PG0358 Genetic Counseling; o PG0364 Gene Expression Profiling for Cancers of Unknown Primary Site (81504, 81540); o PG0374 Verifi Prenatal Test (81420, 81507, 0009M); o PG0387 Genetic Testing for Cystic Fibrosis (81220-81224); o PG0391 UGT1A1 Targeted Mutation Analysis for Irinotecan Response (81350); o PG0398 Genetic Testing for Spinal Muscular Atrophy (81400, 81401, 81403, 81405); o PG0412 Genetic Testing for Macular Degeneration (81401, 81405, 81408); PG0436 CYP2C19 & CYP2D6 Pharmacogenetic Testing (81225, 81226); o PG0437 HLA-B1502 & HLA-B5701 Pharmacogenetic Testing (81381); & o PG0438 Next Generation Sequencing (NGS) Tests for Advanced Cancer (81455, 81479); 08/23/18 o PG0442 Carrier Screening for Genetic Diseases.  Updated title PG0298 from Afirma® Thyroid FNA Analysis to Molecular Markers in Fine Needle Aspirates of Thyroid Nodules.  Removed PG0334 ThyroSeq® v.2 Next Generation Sequencing (added to PG0298).  Removed Proprietary Laboratory Analyses (PLA) Codes (0001U-0044U) from this policy, refer to PG0417 Proprietary Laboratory Analyses (PLA) Codes.  Added effective 1/1/18 new Proprietary MAA code 0011M as non-covered for all product lines.  Added effective 4/1/18 new Proprietary MAA codes 0012M & 0013M as non- covered for all product lines.  Codes 81250 & 81255 are now non-covered for Elite per CMS guidelines.  Code 81438 is now covered with prior authorization for Elite per CMS guidelines.  Policy reviewed and updated to reflect most current clinical evidence per The Technology Assessment Working Group (TAWG).  Added reference to genetic policy PG0453 Germline Multi-Gene Panel Testing.  Updated references to the following genetic policies: o PG0296 Comparative Genomic Hybridization (CGH)/Chromosomal Microarray Analysis (CMA), o PG0067 Genetic Testing for Hereditary Breast and Ovarian Cancer syndrome (HBOC), o PG0302 Genetic Testing for Lynch syndrome/Polyposis Syndromes, o PG0336 PTEN Genetic Testing, o PG0287 Non-Invasive Prenatal Screening (NIPS)/Cell-Free Screening for Fetal 7/22/19 Aneuploidy, o PG0387 Cystic Fibrosis Genetic Testing, PG0398 Genetic Testing for Spinal Muscular Atrophy, o PG0360 Fragile X-Related Disorders, o PG0411 Genetic Testing for Dystriphinopathies (Duchenne and Becker Muscular Dystrophy), o PG0375 Molecular Cytogenetic Testing, and o PG0442 Carrier Screening for Genetic Disease.

PG0041 – 08/06/2021  Deleted specific gene names under 81400-81408, 81479 that were listed as not meeting medical necessity.  Added CPT codes 81163-81167, 81329, 81336, and 81337, which all require prior authorization.  Deleted CPT codes 81211, 81213, and 81214 to reflect changes in the CPT Coding Expert Manual.  CPT codes 81410, 81412, 81430-81436, 81438, 81440, 81442, 81460, 81465, 81470, 81471 were Previously non-covered for HMO, PPO, Individual, Marketplace, and Elite plans.  The policy was updated to reference PG0453 Germline Multi-Gene Panel Testing.  Deleted reference to 0004M as medical policy PG0125 has been retired  Updated policy with all active genetic codes related to the policy, including CPT genetic 4/1/2020 PLA U-codes  Policy corrections and updates.  Procedure G0452 was switched from Prior Authorization required to Non-covered for the Advantage Product line in error. Correction made.  Additionally, a review/determination made to allow coverage for the Commercial product lines with a Prior Authorization. 5/8/2020  Additionally procedures 0111U and 0171U were added as covered with a Prior Authorization for the Elite Product line per https://www.cms.gov/files/document/mm11749.pdf , and click on this link, https://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/CR11749.zip.  Additional review/determination to also allow coverage for 0171U for the Commercial product lines 12/14/2020  Medical policy placed on a new Paramount medical policy format  2021 new codes added to the medical policy along with coverage and prior authorizations determinations-see table above. o Procedure 0047U coverage change from Non-Covered to requires a Prior Authorization required for the Advantage Product line, effective 04/01/2021. o Procedures 81168, 81191, 81192, 81193, 81194, 81351, 81353, require a prior authorization, ALL product lines, effective 04/01/2021. o Procedures 81278, 81279, 81338, 81339, 81347, 81348, 81352, 81357, 81360, do not require a prior authorization, ALL product lines, effective 01/01/2021. 02/21/2021 o Procedures 81554, 0173U, 0174U, 0175U, 0177U, 0179U, 0180U, 0181U, 0182U, 0183U, 0184U, 0185U, 0186U, 0187U, 0188U, 0189U, 0190U, 0191U, 0192U, 0193U, 0194U, 0195U, 0196U, 0197U, 0198U, 0199U, 0200U, 0201U, 0203U, 0204U, 0205U, 0208U, 0209U, 0211U, 0212U, 0213U, 0214U, 0215U, 0216U, 0217U, 0218U, 0220U, 0221U, 0222U, 0229U, 0230U, 0231U, 0232U, 0233U, 0234U, 0235U, 0236U, 0237U, 0238U, 0239U are Non-Covered, ALL product lines, effective 01/01/2021. o Procedure 0172U requires a prior authorization for Commercial and Elite/ProMedica Medicare product lines, effective 04/01/2021. Procedure 0172U is Non-Covered, Advantage product line, effective 01/01/2021.  Per updated ODM 4/1/2021 fee schedule, procedures 0090U, 0172U and 81554 now require a prior authorization coverage for the Advantage product line.  Add procedure 0245U, effective 04/01/2021  Procedure 0208U changed to require a prior authorization for Commercial and Elite/ProMedica Medicare per CMS coverage determination. 02/26/2021  Procedure 81552 added to/addressed in medical policy PG0119 Gene Expression Profiling of Melanomas. Additionally, procedures 0090U and 81529 addressed in medical policy PG0019 Gene Expression Profiling of Melanomas.  Procedures 81210, 81406, 81445, 81479, 81545, 81546, 81599, 0018U, 0026U, 0204U, 0208U, 0245U addressed in updated/revised medical policy PG0298 Molecular Markers in Fine Needle Aspirates of Thyroid Nodules

PG0041 – 08/06/2021  Procedure 81419 added to medical policy PG0041 and to medical policies, PG0453 & PG0467 as covered prior authorization required effective 5/1/2021.  Procedure 81546 replaced for end-dated procedure 81545  Additionally medical policy PG0298 Molecular Markers in Fine Needle Aspirates of Thyroid Nodules updated with procedure 81546  Added unlisted procedure 81479 to the table, indicating prior authorization required for all product 04/11/2021 lines. Note: it was already listed in the green box under other medical policies as requiring a prior authorization.  Added documentation indicating that a prior authorization is required for all genetic testing unless 08/06/2021 specifically indicated otherwise, no matter the diagnosis.

REFERENCES/RESOURCES Centers for Medicare and Medicaid Services, CMS Manual System and other CMS publications and services

Ohio Department of Medicaid

American Medical Association, Current Procedural Terminology (CPT®) and associated publications and services

Centers for Medicare and Medicaid Services, Healthcare Common Procedure Coding System, HCPCS Release and Code Sets

Hayes, Inc.

Industry Standard Review

PG0041 – 08/06/2021