Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code (DMD) (e.g., Duchenne/Becker muscular dystrophy) deletion analysis and 81161 duplication analysis, if performed Aspartoacylase (ASPA) (e.g., Canavan disease) analysis, common variants (e.g., E285A, 81200 Y231X) Adenomatous polyposis coli (APC) (e.g., familial adenomatous polyposis [FAP], attenuated 81201 FAP) gene analysis; full gene sequence 81202 APC (e.g., FAP, attenuated FAP) gene analysis; known familial variants

81203 APC (e.g., FAP, attenuated FAP) gene analysis; duplication/deletion variants

Branched-chain keto acid dehydrogenase E1, beta polypeptide (BCKDHB) (e.g., Maple syrup 81205 urine disease) gene analysis, common variants (e.g., R183P, G278S, E422X) BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; major 81206 breakpoint, qualitative or quantitative BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; minor 81207 breakpoint, qualitative or quantitative BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; other 81208 breakpoint, qualitative or quantitative Bloom syndrome, RecQ helicase-like (BLM) (e.g., Bloom syndrome) gene analysis, 81209 2281del6ins7 variant BRAF (v-raf murine sarcoma viral oncogene homolog B1) (e.g., colon cancer), gene analysis, 81210 V600E variant Breast cancer 1 and 2 (BRCA1, BRCA2) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants in BRCA1 (i.e., 81211 exon 13 del 3.835kb, exon 13 dup 6kb, exon 14-20 del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb) BRCA1, BRCA2 (e.g., hereditary breast and ovarian cancer) gene analysis; 185delAG, 81212 5385insC, 6174delT variants BRCA1, BRCA2 (e.g., hereditary breast and ovarian cancer) gene analysis; uncommon 81213 duplication/deletion variants BRCA1 (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and 81214 common duplication/deletion variants (i.e., exon 13 del 3.835kb, exon 13 dup 6kb, exon 14- 20 del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb)

81215 BRCA1 (e.g., hereditary breast and ovarian cancer) gene analysis; known familial variant 81216 BRCA2 (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis 81217 BRCA2 (e.g., hereditary breast and ovarian cancer) gene analysis; known familial variant transmembrane conductance regulator (CFTR) (e.g., cystic fibrosis) gene 81220 analysis; common variants (e.g., ACMG/ACOG guidelines) 81221 CFTR (e.g., cystic fibrosis) gene analysis; known familial variants

81222 CFTR (e.g., cystic fibrosis) gene analysis; duplication/deletion variants

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code

81223 CFTR (e.g., cystic fibrosis) gene analysis; full gene sequence

81224 CFTR (e.g., cystic fibrosis) gene analysis; intron 8 poly-T analysis (e.g., male infertility) Cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) (e.g., drug metabolism), 81225 gene analysis, common variants (e.g., *2, *3, *4, *8, *17) Cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) (e.g., drug metabolism), 81226 gene analysis, common variants (e.g., *2, *3, *4, *5, *6, *9, *10, *17, *19, *29, *35, *41, *1XN, *2XN, *4XN) Cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) (e.g., drug metabolism), 81227 gene analysis, common variants (e.g., *2, *3, *5, *6) Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic 81228 regions for copy number variants (e.g., bacterial artificial [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis) Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic 81229 regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities Epidermal growth factor receptor (EGFR) (e.g., non-small cell lung cancer) gene analysis, 81235 common variants (e.g., exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q) F2 (prothrombin, coagulation factor II) (e.g., hereditary hypercoagulability) gene analysis, 81240 20210G>A variant 81241 F5 (coagulation factor V) (e.g., hereditary hypercoagulability) gene analysis, Leiden variant Fragile X mental retardation 1 (FMR1) (e.g., fragile X mental retardation) gene analysis; 81243 evaluation to detect abnormal (e.g., expanded) alleles FMR1 (e.g., fragile X mental retardation) gene analysis; characterization of alleles (e.g., 81244 expanded size and methylation status) Fms-related tyrosine kinase 3 (FLT3) (e.g., acute myeloid leukemia), gene analysis, internal 81245 tandem duplication (ITD) variants (ie, exons 14, 15) Glucose-6-phosphatase, catalytic subunit (G6PC) (e.g., Glycogen storage disease, Type 1a, 81250 von Gierke disease) gene analysis, common variants (e.g., R83C, Q347X) Glucosidase, beta, acid (GBA) (e.g., Gaucher disease) gene analysis, common variants (e.g., 81251 N370S, 84GG, L444P, IVS2+1G>A) , beta 2 (GJB2), 26kDa, 26 (e.g., nonsyndromic hearing loss) 81252 gene analysis; full gene sequence 81253 GJB2 (e.g., nonsyndromic hearing loss) gene analysis; known familial variants , beta 6 (GJB6), 30kDa, connexin 30 (e.g., nonsyndromic hearing loss) 81254 gene analysis, common variants (e.g., 309kb [del(GJB6-D13S1830)] and 232kb [del(GJB6- D13S1854)]) Hexosaminidase A (HEXA [alpha polypeptide]) (e.g., Tay-Sachs disease) gene analysis, 81255 common variants (e.g., 1278insTATC, 1421+1G>C, G269S) Hemochromatosis (HFE) (e.g., hereditary hemochromatosis) gene analysis, common variants 81256 (e.g., C282Y, H63D)

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code Alpha globin 1 and alpha globin 2 (HBA1/HBA2) (e.g., alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis, for common deletions or variant (e.g., 81257 Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5 and Constant Spring) Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated 81260 protein (IKBKAP) (e.g., familial dysautonomia) gene analysis, common variants (e.g., 2507+6T>C, R696P) Immunoglobulin heavy chain locus (IGH@) (e.g., leukemias and lymphomas, B-cell), gene 81261 rearrangement analysis to detect abnormal clonal population(s); amplified methodology (e.g., polymerase chain reaction) IGH@ (e.g., leukemias and lymphomas, B-cell), gene rearrangement analysis to detect 81262 abnormal clonal population(s); direct probe methodology (e.g., Southern blot)

81263 IGH@ (e.g., leukemia and lymphoma, B-cell), variable region somatic mutation analysis IGK@ (e.g., leukemia and lymphoma, B-cell), gene rearrangement analysis, evaluation to 81264 detect abnormal clonal population(s) Comparative analysis using short tandem repeat (STR) markers; patient and comparative specimen (e.g., pretransplant recipient and donor germline testing, post-transplant non- 81265 hematopoietic recipient germline [e.g., buccal swab or other germline tissue sample] and donor testing, twin zygosity testing or maternal cell contamination of fetal cells) Comparative analysis using STR markers; each additional specimen (e.g., additional cord 81266 blood donor, additional fetal samples from different cultures, or additional zygosity in multiple birth pregnancies) (List separately in addition to code for primary procedure) Chimerism (engraftment) analysis, post transplantation specimen (e.g., hematopoietic stem 81267 cell), includes comparison to previously performed baseline analyses; without cell selection Chimerism (engraftment) analysis, post transplantation specimen (e.g., hematopoietic stem 81268 cell), includes comparison to previously performed baseline analyses; with cell selection (e.g., CD3, CD33), each cell type Janus kinase 2 (JAK2) (e.g., myeloproliferative disorder) gene analysis, p.Val617Phe (V617F) 81270 variant KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene) (e.g., carcinoma) gene analysis, variants 81275 in codons 12 and 13 Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, 81280 CACNA1C, CAV3, SCN4B, AKAP, SNTA1 and ANK2); full sequence analysis Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, 81281 CACNA1C, CAV3, SCN4B, AKAP, SNTA1 and ANK2); known familial sequence variant Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, 81282 CACNA1C, CAV3, SCN4B, AKAP, SNTA1 and ANK2); duplication/deletion variants Mucolipin 1 (MCOLN1) (e.g., Mucolipidosis, type IV) gene analysis, common variants (e.g., 81290 IVS3-2A>G, del6.4kb) 5,10-methylenetetrahydrofolate reductase (MTHFR) (e.g., hereditary hypercoagulability) 81291 gene analysis, common variants (e.g., 677T, 1298C) MutL homolog 1 (MLH1, colon cancer, non-polyposis type 2) (e.g., hereditary non-polyposis 81292 colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code MLH1 (colon cancer, non-polyposis type 2) (e.g., hereditary non-polyposis colorectal cancer, 81293 Lynch syndrome) gene analysis; known familial variants MLH1 (colon cancer, non-polyposis type 2) (e.g., hereditary non-polyposis colorectal cancer, 81294 Lynch syndrome) gene analysis; duplication/deletion variants MutS homolog 2 (MSH2, colon cancer, non-polyposis type 1) (e.g., hereditary non-polyposis 81295 colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MSH2 (colon cancer, non-polyposis type 1) (e.g., hereditary non-polyposis colorectal cancer, 81296 Lynch syndrome) gene analysis; known familial variants MSH2 (colon cancer, non-polyposis type 1) (e.g., hereditary non-polyposis colorectal cancer, 81297 Lynch syndrome) gene analysis; duplication/deletion variants MutS homolog 6 (MSH6 [E. coli]) (e.g., hereditary non-polyposis colorectal cancer, Lynch 81298 syndrome) gene analysis; full sequence analysis MSH6 (E. coli) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene 81299 analysis; known familial variants MSH6 (E. coli) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene 81300 analysis; duplication/deletion variants Microsatellite instability analysis (e.g., hereditary non-polyposis colorectal cancer, Lynch 81301 syndrome) of markers for mismatch repair deficiency (e.g., BAT25, BAT26), includes comparison of neoplastic and normal tissue, if performed Methyl CpG binding protein 2 (MECP2) (e.g., Rett syndrome) gene analysis; full sequence 81302 analysis 81303 MECP2 (e.g., Rett syndrome) gene analysis; known familial variant 81304 MECP2 (e.g., Rett syndrome) gene analysis; duplication/deletion variants 81310 Nucleophosmin (NPM1) (e.g., acute myeloid leukemia) gene analysis, exon 12 variants Promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha), (t(15;17)) (e.g., 81315 promyelocytic leukemia) translocation analysis; common breakpoints (e.g., intron 3 and intron 6), qualitative or quantitative

81316 PML/RARalpha, (t(15;17)), (e.g., promyelocytic leukemia) translocation analysis; single breakpoint (e.g., intron 3, intron 6 or exon 6), qualitative or quantitative

81317 Postmeiotic segregation increased 2 (S. cerevisiae) (PMS2) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis PMS2 (S. cerevisiae) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene 81318 analysis; known familial variants PMS2 (S. cerevisiae) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene 81319 analysis; duplication/deletion variants Phosphatase and tensin homolog (PTEN) (e.g., Cowden syndrome, PTEN hamartoma tumor 81321 syndrome) gene analysis; full sequence analysis PTEN (e.g., Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; known 81322 familial variant PTEN (e.g., Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; 81323 duplication/deletion variant

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code Peripheral myelin protein 22 (PMP22) (e.g., Charcot-Marie-Tooth, hereditary neuropathy 81324 with liability to pressure palsies) gene analysis; duplication/deletion analysis PMP22 (e.g., Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) 81325 gene analysis; full sequence analysis PMP22 (e.g., Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) 81326 gene analysis; known familial variant

81330 Sphingomyelin phosphodiesterase 1 (SMPD1, acid lysosomal) (e.g., Niemann-Pick disease, Type A) gene analysis, common variants (e.g., R496L, L302P, fsP330) Small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A 81331 (SNRPN/UBE3A) (e.g., Prader-Willi syndrome and/or Angelman syndrome), methylation analysis Serpin peptidase inhibitor, clade A, alpha-1 antiproteinase, antitrypsin, member 1 81332 (SERPINA1) (e.g., alpha-1-antitrypsin deficiency), gene analysis, common variants (e.g., *S and *Z) T cell antigen receptor, beta (TRB@) (e.g., leukemia and lymphoma), gene rearrangement 81340 analysis to detect abnormal clonal population(s); using amplification methodology (e.g., polymerase chain reaction) TRB@ (e.g., leukemia and lymphoma), gene rearrangement analysis to detect abnormal 81341 clonal population(s); using direct probe methodology (e.g., Southern blot) TRG@ (e.g., leukemia and lymphoma), gene rearrangement analysis, evaluation to detect 81342 abnormal clonal population(s) UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) (e.g., irinotecan 81350 metabolism), gene analysis, common variants (e.g., *28, *36, *37) Vitamin K epoxide reductase complex, subunit 1 (VKORC1) (e.g., warfarin metabolism), gene 81355 analysis, common variants (e.g., -1639/3673) Molecular pathology procedure, Level 1 (e.g., identification of single germline variant [e.g., SNP] by techniques such as restriction enzyme digestion or melt curve analysis) acyl-CoA dehydrogenase, C-4 to C-12 straight chain, MCAD (ACADM) (e.g., medium chain acyl dehydrogenase deficiency), K304E variant angiotensin converting enzyme (ACE) (e.g., hereditary blood pressure regulation), insertion/deletion variant angiotensin II receptor, type 1 (AGTR1) (e.g., essential hypertension), 1166A>C variant chemokine C-C motif receptor 5 (CCR5) (e.g., HIV resistance), 32-bp deletion mutation/794 825del32 deletion dihydropyrimidine dehydrogenase (DPYD) (e.g., 5-fluorouracil/5-FU and capecitabine drug metabolism), IVS14+1G>A variant F2 (coagulation factor 2) (e.g., hereditary 81400 hypercoagulability), 1199G>A variant F5 (coagulation factor V) (e.g., hereditary hypercoagulability), HR2 variant F7 (coagulation factor VII [serum prothrombin conversion accelerator]) (e.g., hereditary hypercoagulability), R353Q variant F13B (coagulation factor XIII, B polypeptide) (e.g., hereditary hypercoagulability), V34L variant fibrinogen beta chain (FGB) (e.g., hereditary ischemic heart disease), -455G>A variant Human Platelet Antigen 1 genotyping (HPA-1), integrin, beta 3 (ITGB3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (e.g., neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-1a/b (L33P) Human Platelet Antigen 2 genotyping (HPA-2), glycoprotein Ib (GP1BA [platelet], alpha polypeptide [GPIba]) (e.g., neonatal alloimmune thrombocytopenia [NAIT], post- transfusion purpura), HPA-2a/b (T145M) Human Platelet Antigen 3 genotyping (HPA-3),

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code integrin, alpha 2b (ITGA2B [platelet glycoprotein IIb of IIb/IIIa complex], antigen CD41 [GPIIb]) (e.g., neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), HPA-3a/b (I843S) Human Platelet Antigen 4 genotyping (HPA-4), integrin, beta 3 (ITGB3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (e.g., NAIT, post-transfusion purpura), HPA-4a/b (R143Q) Human Platelet Antigen 5 genotyping (HPA-5), integrin, alpha 2 (ITGA2 [CD49B, alpha 2 subunit of VLA-2 receptor] [GPIa]) (e.g., NAIT, post-transfusion purpura), HPA-5a/b (K505E) Human Platelet Antigen 6 genotyping (HPA-6w), ITGB3 (platelet glycoprotein IIIa, antigen CD61 [GPIIIa]) (e.g., NAIT, post-transfusion purpura), HPA-6a/b (R489Q) Human Platelet Antigen 9 genotyping (HPA-9w), integrin, alpha 2b (ITGA2B [platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41] [GPIIb]) (e.g., NAIT, post-transfusion purpura), HPA-9a/b (V837M) Human Platelet Antigen 15 genotyping (HPA-15), CD109 (CD109 molecule) (e.g., NAIT, post-transfusion purpura), HPA-15a/b(S682Y) serpine peptidase inhibitor clade E, member 1, plasminogen activator inhibitor -1, PAI-1 (SERPINE1) (e.g., thrombophilia), 4G variant Molecular pathology procedure, Level 2 (e.g., two to 10 SNPs, one methylated variant or one somatic variant [typically using nonsequencing target variant analysis], or detection of a dynamic mutation disorder/triplet repeat) ABL (c-abl oncogene 1, receptor tyrosine kinase) (e.g., acquired imatinib resistance), T315I variant ACADM (acyl-CoA dehydrogenase, C-4 to C- 12 straight chain, MCAD) (e.g., medium chain acyl dehydrogenase deficiency), common variants (e.g., K304E, Y42H) ADRB2 (adrenergic beta-2 receptor surface) (e.g., drug metabolism), common variants (e.g., G16R, Q27E) APOE (apolipoprotein E) (e.g., hyperlipoproteinemia type III, cardiovascular disease, alzheimer’s disease), common variants (e.g., *2, *3, *4) CBFB/MYH11 (inv(16)) (e.g., acute myeloid leukemia), qualitative and quantitative, if performed CCND1/IGH (BCL1/IgH, t(11;14)) (e.g., mantle cell lymphoma) translocation analysis, major breakpoint, qualitative and quantitative, if performed CFH/ARMS2 (complement factor H/age-related maculopathy susceptibility 2) (e.g., macular degeneration), common variants (e.g., Y402H [CFH], A69S [ARMS2]) CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (e.g., drug metabolism), common variants (e.g., *2, *3, *4, *5, *6) CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5) (e.g., 81401 drug metabolism), common variants (e.g., *2, *3, *4, *5, *6) DMPK (dystrophia myotonica- protein kinase) (e.g., myotonic dystrophy, type 1), evaluation to detect abnormal (e.g., expanded) alleles F11 (coagulation factor XI) (e.g., coagulation disorder), common variants (e.g., E117X [Type II], F283L [Type III], IVS14del14, and IVS14+1G>A [Type I]) FGFR3 (fibroblast growth factor receptor 3) (e.g., achondroplasia), common variants (e.g., 1138G>A, 1138G>C) FIP1L1/PDGFRA (del[4q12]) (e.g., imatinib-sensitive chronic eosinophilic leukemia), qualitative and quantitative, if performed GALT (galactose-1-phosphate uridylyltransferase) (e.g., galactosemia), common variants (e.g., Q188R, S135L, K285N, T138M, L195P, Y209C, IVS2-2A>G, P171S, del5kb, N314D, L218L/N314D) HBB (hemoglobin, beta) (e.g., sickle cell anemia, hemoglobin C, hemoglobin E), common variants (e.g., HbS, HbC, HbE) HTT (huntingtin) (e.g., Huntington disease), evaluation to detect abnormal (e.g., expanded) alleles RUNX1/RUNX1T1 (t(8;21)) (e.g., acute myeloid leukemia) translocation analysis, qualitative, and quantitative, if performed SEPT9 (Septin 9) (e.g., colon cancer), methylation analysis TPMT (thiopurine S-methyltransferase) (e.g., drug metabolism), common variants (e.g., *2, *3) VWF (von Willebrand factor) (e.g., von Willebrand disease type 2N), common variants (e.g., T791M, R816W, R854Q)

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code Molecular pathology procedure, Level 3 (e.g., greater than 10 SNPs, 2-10 methylated variants or 2-10 somatic variants [typically using non-sequencing target variant analysis], immunoglobulin and T-cell receptor gene rearrangements, duplication/deletion variants 1 exon) CYP21A2 (cytochrome P450, family 21, subfamily A, polypeptide 2) (e.g., congenital adrenal hyperplasia, 21-hydroxylase deficiency), common variants (e.g., IVS2-13G, P30L, I172N, exon 6 mutation cluster [I235N, V236E, M238K], V281L, L307FfsX6, Q318X, R356W, P453S, G110VfsX21, 30-kb deletion variant) ESR1/PGR (receptor 1/progesterone receptor) 81402 ratio (e.g., breast cancer) KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (e.g., mastocytosis), common variants (e.g., D816V, D816Y, D816F) MEFV (Mediterranean fever) (e.g., familial Mediterranean fever), common variants (e.g., E148Q, P369S, F479L, M680I, I692del, M694V, M694I, K695R, V726A, A744S, R761H) MPL (myeloproliferative leukemia virus oncogene, thrombopoietin receptor, TPOR) (e.g., myeloproliferative disorder), common variants (e.g., W515A, W515K, W515L, W515R) TRD@ (T cell antigen receptor, delta) (e.g., leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population Molecular pathology procedure, Level 4 (e.g., analysis of single exon by DNA sequence analysis, analysis of greater than 10 amplicons using multiplex PCR in two or more independent reactions, mutation scanning or duplication/deletion variants of two to five exons) c-abl oncogene 1, receptor tyrosine kinase (ABL1) (e.g., acquired imatinib tyrosine kinase inhibitor resistance), variants in the kinase domain deleted in azoospermia and sex determining region Y (DAZ/SRY) (e.g., male infertility), common deletions (e.g., AZFa, AZFb, AZFc, AZFd) gap junction protein, beta 1 (GJB1) (e.g., Charcot-Marie-Tooth X-linked), full 81403 gene sequence (Janus kinase 2 (JAK2) (e.g., myeloproliferative disorder), exon 12 sequence and exon 13 sequence, if performed KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene) (e.g., carcinoma), gene analysis, variant(s) in exon 2 MPL (myeloproliferative leukemia virus oncogene, thrombopoietin receptor, TPOR) (e.g., myeloproliferative disorder), exon 10 sequence von Hippel-Lindau tumor suppressor (VHL) (e.g., von Hippel-Lindau familial cancer syndrome), deletion/duplication analysis von Willebrand factor (VWF) (e.g., von Willebrand disease types 2A, 2B, 2M), targeted sequence analysis (e.g., exon 28) Molecular pathology procedure, Level 5 (e.g., analysis of two to five exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of sixe to 10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis) biotinidase (BTD) (e.g., biotinidase deficiency), full gene sequence cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) (e.g., primary congenital glaucoma), full gene sequence dystrophia myotonica-protein kinase (DMPK) (e.g., myotonic dystrophy type 1), characterization of abnormal (e.g., expanded) alleles early growth response 2 (EGR2) (e.g., 81404 Charcot-Marie-Tooth), full gene sequence fukutin related protein (FKRP) (e.g., congenital muscular dystrophy type 1C [MDC1C], limb-girdle muscular dystrophy [LGMD] type 2I), full gene sequence forkhead box G1 (FOXG1) (e.g., Rett syndrome), full gene sequence facioscapulohumeral muscular dystrophy 1A (FSHMD1A) (e.g., facioscapulohumeral muscular dystrophy), evaluation to detect abnormal (e.g., deleted) alleles FSHMD1A (e.g., facioscapulohumeral muscular dystrophy), characterization of haplotype(s) (i.e., chromosome 4A and 4B haplotypes) HBB (hemoglobin, beta, Beta-Globin) (e.g., thalassemia), full gene sequence KIT (C-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code oncogene homolog) (e.g., GIST, acute myeloid leukemia, melanoma), targeted gene analysis (e.g., exons 8, 11, 13, 17, 18) LITAF (lipopolysaccharide-induced TNF factor) (e.g., Charcot- Marie-Tooth), full gene sequence MEFV (Mediterranean fever) (e.g., familial Mediterranean fever), full gene sequence neuroblastoma RAS viral oncogene homolog (NRAS) (e.g., colorectal carcinoma), exon 1 and exon 2 sequences platelet-derived growth factor receptor alpha polypeptide (PDGFRA) (e.g., gastrointestinal stromal tumor), targeted sequence analysis (e.g., exons 12, 18) ret proto-oncogene (RET) (e.g., multiple endocrine neoplasia, type 2B and familial medullary thyroid carcinoma), common variants (e.g., M918T, 2647_2648delinsTT, A883F) SDHD (succinate dehydrogenase complex, subunit D, integral ) (e.g., hereditary paraganglioma), full gene sequence VHL tumor suppressor (e.g., von Hippel-Lindau familial cancer syndrome), full gene sequence VWF (e.g., von Willebrand disease type 1C), targeted sequence analysis (e.g., exons 26, 27, 37)

Molecular pathology procedure, Level 6 (e.g., analysis of six to 10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 11 to 25 exons) cytochrome P450, family 21, subfamily A, polypeptide2 (CYP21A2) (e.g., steroid 21-hydroxylase isoform, congenital adrenal hyperplasia), full gene sequence fukutin (FKTN) (e.g., limb-girdle muscular dystrophy [LGMD] type 2M or 2L), full gene sequence myelin protein zero (MPZ) (e.g., Charcot-Marie-Tooth), full gene sequence , light polypeptide (NEFL) (e.g., Charcot-Marie-Tooth), full gene sequence ret proto-oncogene (RET) (e.g., multiple endocrine neoplasia, type 2A and familial medullary thyroid carcinoma), targeted sequence analysis 81405 (e.g., exons 10, 11, 13-16) succinate dehydrogenase complex, subunit B, iron sulfur (SDHB) (e.g., hereditary paraganglioma), full gene sequence transforming growth factor, beta receptor 1 (TGFBR1) (e.g., Marfan syndrome), full gene sequence transforming growth factor, beta receptor 2 (TGFBR2) (e.g., Marfan syndrome), full gene sequence thyroid hormone receptor, beta (THRB) (e.g., thyroid hormone resistance, thyroid hormone beta receptor deficiency), full gene sequence or targeted sequence analysis of greater than five exons tumor protein 53 (TP53) (e.g., Li-Fraumeni syndrome, tumor samples), full gene sequence or targeted sequence analysis of greater than five exons VWF (e.g., von Willebrand disease type 2N), targeted sequence analysis (e.g., exons 18 to 20, 23 to 25)

Molecular pathology procedure, Level 7 (e.g., analysis of 11 to 25 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 26 to 50 exons, cytogenomic array analysis for neoplasia) 3 (CAPN3) (e.g., limb-girdle muscular dystrophy [LGMD] type 2A, calpainopathy), full gene sequence cytogenomic microarray analysis, neoplasia (e.g., interrogation of copy number, and loss-of-heterozygosity via single nucleotide polymorphism [SNP]-based comparative genomic hybridization [CGH] microarray analysis) GALT (galactose-1-phosphate uridylyltransferase) (e.g., galactosemia), full gene sequence 81406 HEXA (hexosaminidase A, alpha polypeptide) (e.g., Tay-Sachs disease), full gene sequence LMNA ( A/C) (e.g., Emery-Dreifuss muscular dystrophy [EDMD1, 2 and 3] limb-girdle muscular dystrophy [LGMD] type 1B, dilated cardiomyopathy [CMD1A], familial partial lipodystrophy [FPLD2]), full gene sequence PAH (phenylalanine hydroxylase) (e.g., phenylketonuria), full gene sequence polymerase (DNA directed), gamma (POLG) (e.g., Alpers-Huttenlocher syndrome, autosomal dominant progressive external ophthalmoplegia), full gene sequence POMGNT1 (protein O-linked mannose beta1,2-N

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code acetylglucosaminyltransferase) (e.g., muscle-eye-brain disease, Walker-Warburg syndrome), full gene sequence protein-O-mannosyltransferase 1 (POMT1) (e.g., limb-girdle muscular dystrophy [LGMD] type 2K, Walker-Warburg syndrome), full gene sequence protein-O- mannosyltransferase 2 (POMT2) (e.g., limb-girdle muscular dystrophy [LGMD] type 2N, Walker-Warburg syndrome), full gene sequence 1 (RYR1, skeletal) (e.g., ), targeted sequence analysis of exons with functionally confirmed mutations VWF (von Willebrand disease type 2A), extended targeted sequence analysis (e.g., exons 11 to 16, 24 to 26, 51, 52) Molecular pathology procedure, Level 8 (e.g., analysis of 26 to 50 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of greater than 50 exons, 81407 sequence analysis of multiple on 1 platform) channel, voltage-gated, type 1, alpha subunit (SCN1A) (e.g., generalized epilepsy with febrile seizures), full gene sequence Molecular pathology procedure, Level 9 (e.g., analysis of greater than 50 exons in a single gene by DNA sequence analysis) 1 (FBN1) (e.g., Marfan syndrome), full gene 81408 sequence neurofibromin 1 (NF1) (e.g., neurofibromatosis, type 1), full gene sequence (RYR1, skeletal) (e.g., malignant hyperthermia), full gene sequence VWF (e.g., von Willebrand disease types 1 and 3), full gene sequence 81479 Unlisted molecular pathology procedure Cell enumeration using immunologic selection and identification in fluid specimen (e.g., 86152 circulating tumor cells in blood); Cell enumeration using immunologic selection and identification in fluid specimen (e.g., 86153 circulating tumor cells in blood); physician interpretation and report, when required 86386 Nuclear Matrix Protrein 22 (NMP22) qualitative 83080 Assay of b-hexosminidase 86316 Immunoassay of tumor antigen, other antigen, quantitative CA 50-72-4 and 549 88230 Tissue culture for non-neoplastic disorders; lymphocyte 88235 Tissue culture for non-neoplastic disorders; amniotic fluid or chorionic villus cells Chromosome analysis for breakage syndromes; baseline breakage, score 50 to 100 cells, 88248 count 20 cells, two karyotypes (e.g., for ataxia telangiectasia, Fanconi anemia, fragile X) 88261 Chromosome analysis; count five cells, one karyotype, with banding 88262 Chromosome analysis; count 15 to 20 cells, two karyotypes, with banding 88263 Chromosome analysis; count 45 cells for mosaicism, two karyotypes, with banding 88264 Chromosome analysis; analyze 20 to 25 cells Chromosome analysis, amniotic fluid or chorionic villus, count 15 cells, one karyotype, with 88267 banding Chromosome analysis, in situ for amniotic fluid cells, count cells from six to 12 colonies, one 88269 karyotype, with banding 88271 Molecular cytogenetics; DNA probe, each (e.g., FISH) Molecular cytogenetics; chromosomal in situ hybridization, analyze three to five cells (e.g., 88272 for derivatives and markers) Molecular cytogenetics; chromosomal in situ hybridization, analyze 10 to 30 cells (e.g., for 88273 microdeletions)

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code 88274 Molecular cytogenetics; interphase in situ hybridization, analyze 25 to 99 cells 88275 Molecular cytogenetics; interphase in situ hybridization, analyze 100 to 300 cells 88280 Chromosome analysis; additional karyotypes, each study 88283 Chromosome analysis; additional specialized banding technique (e.g., NOR, C-banding) 88285 Chromosome analysis; additional cells counted, each study 88289 Chromosome analysis; additional high-resolution study 88291 Cytogenetics and molecular cytogenetics, interpretation and report 88299 Unlisted cytogenetic study 88360 Alterations p53 gene 88384 Array based analysis of multiple molecular probes, probes one to 10 88385 Array based analysis of multiple molecular probes, probes 11 to 50 88386 Array based analysis of multiple molecular probes, probes 51 to 250 S3800 Genetic testing for ALS S3828 Complete gene sequence analysis; MLH1 gene S3829 Complete gene sequence analysis; MLH2 gene Complete MLH1 and MLH2 gene sequence analysis for hereditary nonpolyposis colorectal S3830 cancer (HNPCC) genetic testing Single-mutation analysis (in individual with a known MLH1 and MLH2 mutation in the family) S3831 for HNPCC genetic testing S3833 Complete APC gene sequence analysis for susceptibility to FAP and attenuated FAP S3835 Complete gene sequence analysis for cystic fibrosis genetic testing S3837 Complete sequence analysis for hemochromotosis genetic testing DNA analysis for germline mutations of the ret-proto-oncogene susceptibility to multiple S3840 endocrine neoplasia type 2 S3841 Genetic testing for retinoblastoma S3842 Genetic testing for von Hippel-Landau disease S3843 DNA analysis for f5 gene for susceptibility for Factor V Leiden thrombophilia S3844 DNA analysis of the connexin 26 gene for susceptibility to congenital profound deafness S3845 Genetic testing for alphathalessemia S3846 Genetic testing for hemoglobin E beta-thalassemia S3847 Genetic testing for Tay-Sachs disease S3848 Genetic testing for Gaucher disease S3849 Genetic testing for Niemann-Pick disease S3850 Genetic testing for sickle cell disease S3851 Genetic testing for Canavan disease S3852 DNA analysis for apoe epilson 4 allele for susceptibility to alzheimer's disease S3853 Genetic testing for myotonic muscular dystrophy S3854 Gene expression profiling panel for use in the management of breast cancer treatment S3855 Genetic testing for detection of mutations in presenlin - one gene S3890 DNA analysis, fecal for CRC screening

GCHHMABHH 1240ALL0613-C Genetic Tests and Disease States Included in Humana’s Genetic Guidance Program

CPT or Current Procedural Terminology (CPT)/Healthcare Common Procedure Coding System HCPCS (HCPCS) Code Description Code Genetic testing, comprehensive cardiac analysis, for variants in five major S3860 cardiac ion channel genes for individuals with high index of suspicion for familial Long QT syndrome or related disorders Genetic testing, , voltage gated, type v, alpha subunit (scn5a) and variants S3861 for suspected Genetic testing, family-specific ion channel analysis, for blood relatives of individuals (index case) who have previously tested positive for a genetic variant or a cardiac ion channel S3862 syndrome using either one of the above test configurations or confirmed results from another laboratory S3865 Comprehensive gene sequence analysis for hypertrophic cardiomyopathy Genetic analysis for a specific gene mutation for hypertrophic cardiomyopathy (HCM) in an S3866 individual with a known HCM mutation in the family Comparative genomic hybrization (CGH) microarray testing for developmental delay, autism S3870 spectrum disorder and/or mental retardation

GCHHMABHH 1240ALL0613-C