Genetic Diagnostics Test(S)/Gene(S)/Panel(S)

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Genetic Diagnostics Test(s)/Gene(s)/Panel(s):

› Analysis Requested Single Gene Sequencing NGS Panel NGS Panel Plus Additional Test Options Sequencing (Sanger) Sequencing Sequencing Hotspot Testing Sequencing (NGS) Sequencing Sequencing Somatic Mutation Analysis Sequencing + CNVs (with NGS) + NGS based CNVs + NGS based CNVs CentoArrayCyto HD Del/Dup (MLPA or qPCR) Del/Dup with MLPA Del/Dup with MLPA CentoArrayCyto 750K Carrier Testing Prenatal Diagnosis

Relative tested at CENTOGENE yes no Maternal Cell Contamination (Prenatal) Gene name Mutation STAT (Rush fee for non-prenatal samples at additional cost) If yes, CENTOGENE ID Relationship to patient

› Patient Information › Physician or Laboratory (Reporting Address) Last Name Name of Physician First Name Clinic Date of Birth M M D D Y Y Y Y Department Sex Male Female Street Street ZIP Code/Town ZIP Code/Town Country Country Phone Fax Your Reference Number E-mail

Sample Collection Date M M D D Y Y Y Y Please note that all diagnostic reports are exclusively available via our online CentoPortal® www.centoportal.com. Additional report recipient(s) can be conveniently added for individual requests via the portal. › Additional Report Recipient Name of Physician › Billing Clinic CENTOGENE Quotation No. Department Invoice to Patient Clinic/Insurance Street Please attach Authorization/Referral ZIP Code/Town Name Country Department Phone Fax Street E-mail ZIP Code/Town Country › For Somatic Mutation Analysis Only VAT No. Phone Fax Year of Tissue Fixation E-mail Type of Fixation Tumor Grading Stage Tissue of Origin › In Case of Direct Billing to the Patient I authorize the physician to request this analysis/these analyses and I am informed about the resulting costs (and possibly applicable German 19% VAT). I herewith undertake to be liable for the payment of any invoice related to this diagnostics and I declare that the address given › I herewith confirm the correctness of the above given information. above is the correct billing address.

Place, Date Place, Date Signature of Patient/Guardian ✘ Signature of Patient/Guardian ✘

› Material Requirements For detailed material requirements, please refer to page The Terms & Conditions of CENTOGENE AG, which are available on 100 and page 101 for specific material requirements. www.centogene.com apply to your order. Your specific order will be invoiced at the We need mandatorily the following pages from you: 1-6. specific prices as listed on www.centogene.com at the time of receipt of your order. Page 1 ACCREDITED V72.1_July2018 CLIA #99D2049715 Information part of consent form for conducting genetic analyses

CENTOGENE requires a signed consent form from the patient in order to be legally able to conduct a genetic analysis. Please ensure that this signed consent form accompanies the sample(s).

Dear patient,

Your physician has recommended a genetic analysis for you (or a person in your Pseudonymisation and Anonymisation: legal custody) to clarify the diagnosis/symptoms stated in the section “declaration Pseudonymisation means the processing of your personal data in a way that the of consent” below. In order to ensure that you have understood the purpose and personal data can no longer be attributed to your person without a certain identifier, significance of a genetic analysis, we have provided information about the testing which is kept separately and protected only by CENTOGENE. “Anonymisation” refers process and potential results below. to the process of rendering your data anonymous, which then does not allow your identification from the anonymous data at all anymore. The purpose of a genetic analysis is to identify the cause of a suspected disease in you or your family by analyzing your genetic material (DNA) for an abnormal Data protection information for patient and physician: change (variant) that could explain the disease you or members of your family are In the following we want to inform you about the processing of personal data during experiencing. and after the performance of the genetic analysis. "Personal data" is understood to mean all information which relates to an identified or identifiable natural person. To In a genetic analysis, depending on the case, you can be tested for: all such collected and processed personal data, the following applies: • A single gene/variant responsible for a specific, suspected genetic disease, or • Multiple genes (gene panels, whole exome or genome sequencing) in parallel. • Controller and responsible entity for the processing of your personal data is CENTOGENE AG, Am Strande 7, 18055 Rostock, represented by the Executive The study material that is needed to perform the genetic analysis is stated in the Board members as can be found on our website (https://www.centogene.com/ test order form and is typically blood or purified DNA, but may also be tissue, saliva about-centogene/team/executive-board.html). You can reach our data protection or buccal swab. officer under the same address with the addition “Attn: Data Protection Officer” or by email [email protected]. Possible results from the genetic analysis: • Patient: By virtue of this consent form and through your physician, we collect A genetic analysis can have one of several outcomes: the following data about you (in each case insofar as provided): personal details • A disease-causing DNA variant is identified confirming the diagnosis and allowing (including name and address), family relations, age/date of birth, gender, ethnicity, appropriate medical management by your physician (if such is available). nationality, insurance information, symptoms and other medical information, • A DNA variant is identified but at this time, there is not enough scientific and disease, the study material / sample with identifiable genetic data, the genetic medical information to determine if this is a disease-causing variant or not. Your analysis results and findings. All your collected data will be stored for as long as physician will discuss such a result with you and explain what further options are indicated in the consent declaration. The data will be processed – partially also available to you. in data centers operated by service providers under our control and instructions • The genetic analysis results in no specific finding that can explain the symptoms. - for the performance of the genetic analysis requested and for informing your This can be due to the current limitations in scientific or medical knowledge and physician of the results of such analysis, in each case on the basis of the consent technology. provided. In case you have consented accordingly, such data will also be stored and processed for those further purposes as specified in the consent declaration. It is important to understand that genetic analyses – even if the result of a specific • Physician: All your collected data will be processed to communicate with you analysis is negative - are not exhaustive and that it is therefore not possible to about the tests and the results, as well as for invoicing, for as long as we keep exclude risks for all possible genetic diseases for yourself and your family members identifiable data about your patients. This takes place on the basis of legal (especially your children). provisions allowing to process personal data for the purpose of performing It is possible that the knowledge of the test results may result in psychological stress a contract and for customer relation management reasons because we have a for you and your family. It is always recommended to discuss the results with your respective legitimate interest. We use data processors, which have been carefully responsible physician. selected and are subject to our instructions and to regular monitoring. Disclosures to data processors may result in such data being processed in countries outside Incidental findings: of the EU (third countries). For each such transmission of data to a third country Genetic analyses, particularly those involving a large number of genes such as whole it is safeguarded that either an adequate level of protection or reasonable exome or genome sequencing, may identify results that are not directly related to guarantees exist; e.g. by concluding a data processing agreement containing EU the actual reason for your testing (incidental findings). However, such findings standard data protection clauses (retrievable at: http://ec.europa.eu/justice/data- could still be of medical importance for you and your family, as they may provide protection/international-transfers/transfer/index_en.htm). information about a risk (that you may not be aware of) for potentially serious, • You (Patient and Physician) do have the following rights regarding personal unavoidable or non-treatable genetic diseases. data relating to you, which you can exercise at any time, e.g. through an email to As part of the optional sections of your consent declaration below, you can decide [email protected]: whether or not and under which circumstances you wish to be informed about such incidental findings. -- Right to be provided with information about and to have access to the personal data stored on you; Family relationship findings: -- Right to have the personal data stored on you rectified or erased; If several family members are tested, the correct interpretation of the results -- Right to obtain restriction of processing your personal data; depends on the provided relationships between family members being accurate. -- Right to object on grounds relating to your particular situation; If the genetic analysis reveals a possibility that there is a discrepancy in the provided -- Right to data-portability (i.e. receive personal data you provided to us in a relationships, CENTOGENE will not inform you, unless in exceptional cases where structured, commonly used and machine-readable format); and this information is absolutely necessary for the completion and correct medical -- Right to withdraw your consent with effect for the future at any time. interpretation of the requested analysis. • You have the right to lodge a complaint with a supervisory authority regarding Use of the health data, sample and test results: the processing of your personal data. The sample and provided data including health data will be used for the requested • You may have further or modified rights under applicable national law, which analysis and along with the test results will be stored and processed in accordance remain unaffected. with your consent declaration below. • For a more detailed and regularly updated information about how we process personal data please visit our Data Protection Statement under Right of withdrawal: www.centogene.com/data-protection. You can withdraw your consent to the analysis with effect for the future at any time in full or in part without providing a reason.

Right not to know: You have the right not to be informed about test results (right not to know) and to stop the testing processes that have been started at any time up to being given the results and to request the destruction of all analysis results. 1/2 Page 2 V7eng_Information_July2018 V72.1_July2018 Declaration of consent

GENETIC ANALYSIS FOR DISEASE: (filled in by the physician)

By signing this declaration of consent I acknowledge that I have received, read and understood the preceding written explanation about genetic analyses. I also received appropriate explanations (from my physician) regarding the genetic basis, the purpose, scope, type and significance of the planned genetic analysis and achievable results, possibilities of prevention/treatment of the possible disease as well as with regard to risks associated with collecting the sample required for the genetic analysis and the knowledge of the results of the genetic analysis. All my questions have been answered and I have had the necessary time to make an informed decision about the genetic analysis.

With my signature below I give my consent or consent on behalf of the patient for whom I am the legal guardian:

(1) to the genetic analysis by CENTOGENE AG, Am Strande 7, 18055 Rostock, Germany, (CENTOGENE) for the disease stated above, (2) to the collection and processing by my physician and CENTOGENE of my “Personal (Health) Data” (meaning in particular and in each case insofar as provided: personal details (including name and address), family relations, age/date of birth, gender, ethnicity, nationality, insurance information, symptoms and other medical information, disease, the study material/sample with identifiable genetic data, the genetic analysis results and findings) as far as required to conduct the genetic analysis including any necessary transfers of my Personal (Health) Data between physician and CENTOGENE across national borders, (3) to the analysis of the obtained sample and its storage for 10 years at CENTOGENE together with my patient file to be able to verify results of the analysis if need be, (4) to add to my patient file or to files of family members and to use for the above purposes – if applicable – Personal (Health) Data on me or members of my family insofar as they have consented, (5) to inform me or my physician or – if CENTOGENE has been instructed by a laboratory acting on behalf of my physician – such laboratory about the results of the genetic analysis; and (6) to provide upon request to me, my physician or – as the case may be – the requesting laboratory, the raw data of the genetic analysis. MANDATORY

I am aware that I can withdraw my consent with effect for the future in full or in part at any time and that I have the right not to know the results of the genetic analyses as described in the preceding written explanation.

By ticking the relevant “YES/NO” boxes below, I give my additional consent or consent on behalf of the patient for whom I am the legal guardian to:

Reporting of incidental findings Whole exome sequencing (WES) and whole genome sequencing (WGS) tests analyze numerous different genes at the same time. It is therefore possible that a genetic variant found in the genetic analysis is possibly not related to the cause for ordering the testing. These findings, known as incidental findings, can provide information unrelated to your reported clinical symptoms, but can be of medical value for your treatment in the future. I understand the significance of such incidental findings and consent to CENTOGENE reporting DNA variants of the specified classes or YES types in certain genes in accordance with the “ACMG Recommendations for Reporting of Incidental Findings”. I understand that CENTOGENE, using its own discretion, may refrain from reporting the recommended incidental findings or additionally also report (other) non-ACMG recommended NO incidental findings, in each case because of additional scientific and medical information available in CENTOGENE’s databases.

Further storage and use of my Personal (Health) Data and the sample I understand that my Personal (Health) Data and (remaining) sample may help in further research, development and improvement of diagnostic methods and possibly therapeutic solutions. Such measures may in the future also enable and support medical advice and guidance to me and my family members, e.g. related to the diagnosis and treatment of a potential genetic disease.

• I agree that CENTOGENE stores (1) the Personal (Health) Data I provided and information on (affected) family members - if they consented - and the results of the genetic analysis and (2) my sample (including original and processed sample) for a period of 20 years and uses this data and the OPTIONAL remaining samples for the purpose of internal research, improvement, development and validation of analysis procedures and related product and service developments. YES • I agree that after a period of 20 years my Personal (Health) Data and (remaining) sample are anonymized and ownership in the sample is then transferred to CENTOGENE. Both will then remain in CENTOGENE’s archives for use by CENTOGENE without restrictions. • I agree that CENTOGENE may at any time process my anonymized or pseudonymized Personal (Health) Data, e.g. into its databases and datasets NO concerning genetic diseases, for the purpose of scientific and commercial research and to facilitate and contribute to the diagnosis of genetic changes and diseases of other patients. Access to such pseudonymised or anonymised data might be granted to external physicians, scientists and (pharmaceutical) companies for research and development purposes. • I understand that I will not receive any compensation for the use of my Personal (Health) Data or sample by CENTOGENE. • I understand that data in CENTOGENE’s databases – once anonymized - cannot be destroyed upon request as it is unidentifiable and untraceable.

If the undersigning is the legal guardian of the Patient, he/she herewith to confirms to provide the above consent declarations not for himself/herself but on behalf of the respective patient.

Name of Signature of Patient Date Patient /Legal Guardian

I hereby confirm that the consent as shown above has been declared by the patient or (as the case may be) his/her parent or legal guardian and that I have his/her signature on file if it is not shown above. I confirm that the patient is capable of giving this consent (alternatively that the consent was given by a legal guardian of the patient), that all questions of the patient have been answered, that the patient had the necessary time to consider his/her decision and that the patient until now has not exercised his/her right not to know the results of the genetic analyses. I understand that the patient may request to have his/her genetic analyses results eliminated at any time and that I shall forward such requests to CENTOGENE without undue delay. I agree that my own personal data is stored in CENTOGENE’s databases for organizational and invoicing purposes.

Name of Signature of Date Physician Physician

CENTOGENE AG Contact Details Am Strande 7 Phone: +49 (0) 381 80 113 - 416 [email protected] 18055 Rostock, Germany Fax: +49 (0) 381 80 113 - 401 www.centogene.com 2/2 Page 3 V7eng_Consent_July2018 V72.1_July2018 Table of Contents CLINICAL INFORMATION REQUEST

› Metabolic Diseases 6 - 18

› Neurological Diseases 19 - 42

› Ophthalmological Diseases 43 - 48

› Ear, Nose and Throat Diseases 49 - 51

› Bone, Skin and Immune Diseases 52 - 62

› Cardiological Diseases 63 - 68

› Vascular Diseases 69 - 70

› Liver, Kidney and Endocrinological Diseases 71 - 77

› Reproductive Genetics 78

› Haematological Diseases 79 - 83

› Malformation and/or Retardation Syndromes 84 - 95

› Oncogeneticsche Störungen 96 - 99

Contact Details

Customer Service Please send the samples together Tel.: +49 (0)381 80 113- 416 with a completed request form to: Fax: +49 (0)381 80 113- 401 CENTOGENE AG [email protected] Am Strande 7 www.centogene.com 18055 Rostock, Germany

Page 4 V72.1_July2018 MANDATORY

Please provide detailed clinical information Pedigree

Patient name

Age of manifestation Family history:

A. Consanguinity YES NO Unaffected B. Affected siblings YES NO

Clinical information

Please tick the appropriate phenotype(s)

A. NEUROLOGY 7.8 Stroke 2. Skin and integument 3. Endocrine 1. Behavioral abnormality B. METABOLISM 2.1 Abnormal hair 3.1 Diabetes mellitus 1.1 Autism 1. Abnormal creatine kinase 2.2 Abnormal nail 3.2 Hyperparathyroidism

1.2 Attention deficit disorder 2. Decreased plasma carnitine 2.3 Abnormal skin pigmentation 3.3 Hyperthyroidism

1.3 Psychiatric diseases 3. Hyperalaninemia 2.4 Hyperextensible skin 3.4 Hypoparathyroidism

2. Brain imaging 4. Hypoglycemia 2.5 Ichthyosis 3.5 Hypothyroidism 2.1 Abnormal cortical gyration 5. Increased CSF lactate F. CARDIOVASCULAR H. REPRODUCTION 2.2 Abnormal myelination 6. Increased serum pyruvate 1. Angioedema 1. Abnormal external genitalia

2.3 Agenesis of corpus callosum 7. Ketosis 2. Aortic dilatation 2. Abnormal internal genitalia

2.4 Brain atrophy 8. Lactic acidosis 3. Arrhythmia 3. Hypogonadism

2.5 Cerebellar hypoplasia 9. Organic aciduria 4. Atrial septal defect 4. Hypospadias 2.6 Heterotopia C. EYE 5. Coarctation of aorta 5. Infertility 2.7 Holoprosencephaly 1. Blepharospasm 6. Dilated cardiomyopathy I. ONCOLOGY

2.8 Hydrocephalus 2. Cataract 7. Hypertension 1. Adenomatous colonic polyposis

2.9 Leukodystrophy 3. Coloboma 8. Hypertrophic cardiomyopathy 2. Breast carcinoma

2.10 Lissencephaly 4. Glaucoma 9. Hypotension 3. Colorectal carcinoma

3. Developmental delay 5. Microphthalmos 10. Lymphedema 4. Leukemia

3.1 Delayed language dev. 6. Nystagmus 11. Malf. of heart and great vessels 5. Myelofibrosis

3.2 Delayed motor dev. 7. Ophthalmoplegia 12. Myocardial infarction 6. Neoplasm of the lung

3.3 Developmental regression 8. Optic atrophy 13. Stroke 7. Neoplasm of the skin

3.4 Intellectual disability 9. Ptosis 14. Tetralogy of Fallot 8. Paraganglioma

4. Movement abnormality 10. Retinitis pigmentosa 15. Vasculitis 9. Pheochromocytoma

4.1 Ataxia 11. Retinoblastoma 16. Ventricular septal defect J. HEMATOLOGY AND IMMUNOLOGY 4.2 Chorea 12. Strabismus G. GASTROINTESTINAL, 1. Abnormal hemoglobin 4.3 Dystonia 13. Visual impairment GENITOURINARY, ENDOCRINE 2. Abnormality of coagulation 4.4 Parkinsonism D. MOUTH, THROAT AND EAR 1. Gastrointestinal 3. Anemia 5. Neuromuscular abnormality 1. Abnormality of dental color 1.1 Aganglionic megacolon 4. Immunodeficiency

5.1 Hyperreflexia 2. Cleft lip / palate 1.2 Constipation 5. Neutropenia

5.2 Muscle hypertonia 3. Conductive hearing impair. 1.3 Diarrhea 6. Pancytopenia

5.3 Muscle hypotonia 4. External ear malformation 1.4 Gastroschisis 7. Splenomegaly

5.4 Spasticity 5. Hypodontia 1.5 Hepatic failure 8. Thrombocytopenia

6. Seizures 6. Sensoneural hearing impair. 1.6 Hepatomegaly K. PRENATAL AND DEVELOPMENT 6.1 Febrile seizures E. SKIN, INTEGUMENT AND SKELETAL 1.7 High hepatic transaminases 1. Abnormal facial shape 6.2 Focal seizures 1. Skeletal 1.8 Obesity 2. Failure to thrive

6.3 Generalized seizures 1.1 Abnormal limb morphology 1.9 Pyloric stenosis 3. Hemihypertrophy

7. Others 1.2 Abnormal vertebral column 1.10 Vomiting 4. Hydrops fetalis

7.1 Craniosynostosis 1.3 Abnormality of the skeletal system 2. Genitourinary 5. IUGR

7.2 Dementia 1.4 Joint hypermobility 2.1 Abnormal renal morphology 6. Oligohydramnios

7.3 Encephalopathy 1.5 Multiple joint contractures 2.2 Abnormal urinary system 7. Overgrowth

7.4 Headache 1.6 Polydactyly 2.3 Hydronephrosis 8. Polyhydramnios

7.5 Macrocephaly 1.7 Scoliosis 2.4 Renal agenesis 9. Premature birth

7.6 Microcephaly 1.8 Syndactyly 2.5 Renal cyst 10. Short stature

7.7 Migraine 1.9 Talipes equinovarus 2.6 Renal tubular dysfunction 11. Tall stature

Page 5 V72.1_July2018 › Metabolic Diseases - Panels

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code ATP13A2, C19orf12, COASY, CP, DCAF17, Brain iron accumulation syndromes panel PANK2, ATP13A2, PLA2G6 5314 5, 6, 7, 8, 9, 10 FA2H, FTL, PANK2, PLA2G6, SCP2, WDR45 Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes Acid lipase (Wolman), Acidic alpha-glucosidase (Pompe), Acidic sphingomyelinase (Niemann-Pick Type A and Type B), Alpha- fucosidase (Alpha-fucosidase deficiency), Alpha-galactosidase (Fabry), Alpha-L-iduronidase (MPS I), Alpha-mannosidase (Alpha- mannosidase deficiency, ), Alpha-N-ace- tylgalactosaminidase (Schindler/Kanzaki), Arylsulfatase B (MPS VI), Beta-galactosidase (MPS IVB), Beta-glucocerebrosidase and Chi- totriosidase (Gaucher), Beta-glucuronidase CentoLSD Enzyme Panel (MPS VII), Beta-hexosaminidase (Tay-Sachs), 25000 16 Beta-mannosidase (Beta-mannosidase deficiency), Hexosaminidase AB (Sandhoff), Iduronate-2-sulfatase (MPS II), N-acetyl-alpha-glucosaminidase (MPS IIIB), N-acetylgalatosamine-6-sulfate-sulfatase (MPS IVA), Palmitoyl-protein thioesterase (Neuronal ceroid lipofuscinosis type 1, NCL1, Infantile NCL, Santavuori-Haltia disease), Tripeptidyl peptidase (Neuronal ceroid lipofuscinosis type2, NCL2, Late infantile NCL, Jansky- Bielschowsky disease) Acid lipase (Wolman, LIPA), Acidic alpha- glucosidase (Pompe, GAA), Acidic sphingomyelinase (Niemann-Pick Type A and Type B, SMPD1), Alpha-fucosidase (Alpha-fucosidase deficiency, FUCA1), Alpha-galactosidase (Fa- bry, GLA), Alpha-L-iduronidase (MPS I, IDUA), Alpha-mannosidase (Alpha-mannosidase deficiency, MAN2B1), Alpha-N-acetylgala- ctosaminidase (Schindler/Kanzaki, NAGA), Arylsulfatase B (MPS VI, ARSB), Beta-galactosidase (MPS IVB, GLB1), Beta-glucocerebrosidase and Chitotriosidase (Gaucher, GBA), Beta-glucuronidase (MPS VII, GUSB), Beta- CentoLSD Enzyme Panel X-TRA 25001 17 hexosaminidase (Tay-Sachs, HEXA), Beta- mannosidase (Beta-mannosidase deficiency, MANBA), Hexosaminidase AB (Sandhoff, HEXA/HEXB), Iduronate-2-sulfatase (MPS II, IDS), N-acetyl-alpha-glucosaminidase (MPS IIIB, NAGLU), N-acetylgalatosamine-6-sulfate-sulfatase (MPS IVA, GALNS), Palmitoyl- protein thioesterase (Neuronal ceroid lipofuscinosis type 1, NCL1, Infantile NCL, Santavuori-Haltia disease, PPT1), Tripeptidyl peptidase (Neuronal ceroid lipofuscinosis type2, NCL2, Late infantile NCL, Jansky- Bielschowsky disease, TPP1) Alpha-L-iduronidase (MPS I), Iduronate-2-sulfatase (MPS II), N-acetyl-alpha-glucosaminidase (MPS IIIB), N-acetylgalatosamine-6-sul- CentoMPS Enzyme Panel fate-sulfatase (MPS IVA), Beta-galactosidase 25004 16 (MPS IVB), Arylsulfatase B (MPS VI), Beta- glucuronidase (MPS VII), Alpha-mannosidase (Alpha-mannosidase deficiency) Alpha-L-iduronidase (Hurler disease, MPS I, IDUA), Iduronate-2-sulfatase (Hunter disease, MPS II, IDS), N-acetyl-alpha-glucosaminidase (Sanfilippo syndrome, MPS IIIb, NAGLU), N- acetylgalatosamine-6-sulfate-sulfatase (Mor- CentoMPS Enzyme Panel X-TRA quio disease, MPS IVA, GALNS), Beta-galac- 25005 17 tosidase (Morquio disease, MPS IVB, GLB1), Arylsulfatase B (Maroteaux-Lamy syndrome, MPS VI, ARSB), Beta-glucuronidase (Sly syndrome, MPS VII, GUSB), Alpha-mannosidase (Alpha-mannosidase deficiency, MAN2B1) Palmitoyl-protein thioesterase (Neuronal ceroid lipofuscinosis type 1, NCL1, Infantile NCL, Santavuori-Haltia disease) CentoNCL Enzyme Panel 25006 16 Tripeptidyl peptidase (Neuronal ceroid lipofuscinosis type2, NCL2, Late infantile NCL, Jansky-Bielschowsky disease)

Test x Disease Gene OMIM Gene Available test methods code 2-aminoadipic 2-oxoadipic aciduria DHTKD1 2317 614984 2, 4, 7, 8 2-methylbutyrylglycinuria ACADSB 2778 600301 2, 4 3-beta-hydroxysteroid dehydrogenase deficiency type 2 HSD3B2 74 613890 2, 3, 4, 10, 11 3-hydroxy-3-methylglutaryl-CoA lyase deficiency HMGCL 366 613898 2, 3, 4, 10, 11 3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency HMGCS2 2840 600234 2, 4, 10, 11 3-hydroxyisobutryl-CoA hydrolase deficiency HIBCH 2839 610690 2, 4, 7, 8 3-methylglutaconic aciduria type 1 AUH 1350 600529 2, 3, 4, 10, 11 3-methylglutaconic aciduria type 3 OPA3 1402 606580 1, 2, 4, 10, 11 3-methylglutaconic aciduria type 5 DNAJC19 2298 608977 2, 4 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome SERAC1 2299 614725 2, 3, 4, 7, 8, 10, 11 5-oxoprolinase deficiency OPLAH 2855 614243 2, 4, 7, 8 6q24-related transient neonatal diabetes mellitus type 1 UPD chr. 6 3097 10 17-hydroxylation activity deficiency CYP17A1 73 609300 2, 4, 10, 11 Abetalipoproteinemia MTTP 2763 157147 2, 4, 7, 8 Acetycholinesterase deficiency ACHE 2786 100740 2, 4 Acetyl-CoA carboxylase deficiency ACACA 3046 200350 2, 7, 8 Acyl-CoA medium-chain dehydrogenase deficiency ACADM 330 607008 2, 3, 4, 7, 8, 10, 11 Acyl-CoA multiple dehydrogenase deficiency ETFA 332 608053 2, 3, 4, 7, 8, 10, 11 Acyl-CoA multiple dehydrogenase deficiency ETFB 333 130410 2, 3, 4, 10, 11 Acyl-CoA short-chain dehydrogenase deficiency ACADS 334 606885 1, 2, 3, 4, 10, 11 Acyl-CoA very long-chain dehydrogenase deficiency ACADVL 335 609575 2, 4, 7, 8, 10, 11 Adenine phosphoribosyltransferase deficiency APRT 2761 102600 2, 4 Adenylosuccinase deficiency ADSL 1571 608222 2, 4, 7, 8 Adrenal hyperplasia due to 21-hydroxylase deficiency CYP21A2 336 613815 2, 4, 10, 11 Adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency POR 75 124015 2, 4, 7, 8, 10, 11 Adrenal hyperplasia due to steroid 11-beta-hydroxylase deficiency CYP11B1 337 610613 2, 3, 4, 10, 11 Adrenal hypoplasia NR0B1 338 300473 2, 4, 10, 11 Alkaptonuria HGD 16 607474 1, 2, 3, 4, 7, 8, 10, 11 Alpha-2-macroglobulin deficiency A2M 1825 103950 2, 4, 7, 8 Alpha-ketoglutarate dehydrogenase deficiency OGDH 2854 613022 2, 4, 7, 8 Alpha-methylacyl CoA racemase deficiency AMACR 339 604489 2, 3, 4, 10, 11 Aminoacylase deficiency ACY1 1572 104620 2, 4 AMP deaminase deficiency, erythrocytic AMPD3 2254 102772 2, 4, 7, 8 Amyloidosis, familial visceral APOA1 2106 107680 2, 3, 4, 10, 11 Andersen disease GBE1 340 607839 2, 3, 4, 7, 8, 10, 11 Anemia dyserythropoietic type 1A CDAN1 341 607465 2, 3, 4, 7, 8, 10, 11 Anemia dyserythropoietic type 2 SEC23B 342 610512 2, 3, 4, 7, 8, 10, 11 Antitrypsin-alpha-1 deficiency SERPINA1 345 107400 1, 2, 3, 4, 10, 11 Aplastic anemia PRF1 225 170280 2, 4, 10, 11 Aplastic anemia TERC 291 602322 2, 4, 10, 11 Aplastic anemia, SBDS related SBDS 252 607444 2, 3, 4, 10, 11 Apolipoprotein C-II deficiency APOC2 346 608083 2, 3, 4, 10, 11 Apparent mineralocorticoid excess HSD11B2 76 614232 2, 3, 4, 10, 11 Arginase deficiency ARG1 347 608313 2, 4 Arginine-glycine amidinotransferase deficiency GATM 348 602360 2, 3, 4, 10, 11 Argininosuccinic aciduria ASL 349 608310 1, 2, 3, 4, 7, 8, 10, 11 Aromatic L-amino acid decarboxylase deficiency DDC 2835 107930 2, 4, 7, 8 Asparaginesynthetase deficiency ASNS 2013 108370 2, 4 Aspartylglucosaminuria AGA 2244 613228 2, 4 Beta-Galactosamide alpha-2,6-Sialyltransferase 2 deficiency ST6GAL2 2006 608472 2, 4 Beta-ureidopropionase deficiency UPB1 2466 606673 2, 3, 4, 10, 11 Bile acid malabsorption, primary SLC10A2 3044 601295 2, 4 Bile acid synthesis defect type 2, congenital AKR1D1 2779 604741 2, 4 Bile acid synthesis defect type 3, congenital CYP7B1 350 603711 2, 3, 4, 10, 11 Bile acid synthesis defect type 4, congenital AMACR 339 604489 2, 3, 4, 10, 11 Biotinidase deficiency BTD 351 609019 1, 2, 3, 4, 10, 11 Bloom syndrome BLM 352 604610 2, 3, 4, 7, 8, 10, 11 Branched-chain aminotransferase 1 deficiency BCAT1 2656 113520 2, 4, 7, 8 Branched-chain aminotransferase 2 deficiency BCAT2 2657 113530 2, 4 Branched-chain ketoacid dehydrogenase kinase deficiency BCKDK 2795 614901 2, 4 Bronchiectasis with or without elevated sweat chloride type 2 SCNN1A 214 600228 2, 3, 4, 7, 8, 10, 11 Butyrylcholinesterase deficiency BCHE 2741 177400 2, 3, 4, 10, 11

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code ADAR, IFIH1, TREX1, RNASEH2A, RNASEH2B, RNASEH2B, RNASEH2A, TREX1, Aicardi-Goutieres syndrome panel 5036 5, 6, 7, 8, 9, 10 RNASEH2C, SAMHD1 RNASEH2C, SAMHD1 Alzheimer dementia and dementia panel APOE, APP, PRNP, PSEN1, PSEN2, SORL1, TREM2 APP, PSEN1, PSEN2 5090 7, 8, 10 ALS2, ANG, CHCHD10, CHMP2B, DCTN1, ERBB4, FIG4, FUS, HNRNPA1, MATR3, NEFH, Amyotrophic lateral sclerosis (ALS) panel OPTN, PFN1, PRPH, SETX, SIGMAR1, SOD1, SPG11, SETX 5001 7, 8, 10 SPG11, SQSTM1, TARDBP, TBK1, TUBA4A, UBQLN2, VAPB, VCP Bethlem myopathy panel COL6A1, COL6A2, COL6A3, COL12A1 5115 5, 6, 7, 8, 9 CentoArray Cyto™ 750K Genome-wide aCGH with 750,000 markers 50068 7 CentoArray Cyto™ HD Genome-wide aCGH with 2.5 million markers 50001 7 Targets exonic regions of ~6700 genes associa- CentoDx™ Solo 50088 5, 6 ted with known clinical phenotypes Targets exonic regions of ~6700 genes associa- CentoDx™ Trio 50089 5, 6 ted with known clinical phenotypes Targets exonic regions of ~6700 genes associa- CentoDx™ Trio Plus 50090 5 ted with known clinical phenotypes

☐ 1-Hotspot Testing ☐ 2-Carrier Testing (point mutation) ☐ 3-Carrier Testing (del/dup) ☐ 4-Full Gene Sequencing (Sanger) ☐ 5-NGS Panel ☐ 6-NGS Panel + CNV ☐ 7-NGS Panel Plus ☐ 8-NGS Panel Plus + CNV ☐ 9-NGS Panel Genomic ☐ 10-Deletion/Duplication with qPCR/MLPA ☐ 11-Sequencing + Deletion/Duplication ☐ 12-Repeat Expansions Page 23 ☐ 13-Somatic Mutation Analysis ☐ 14-Biochemical Enzyme Analysis ☐ 15-Biomarker Analysis V72.1_July2018 ☐ Biochemical Enzyme Panel ☐ Biochemical Genetics Panel Plus Test x Panel name Genes Available test methods code A2M, AAAS, AANAT, AARS, AARS2, AASS, ABAT, ABCA1, ABCB7, ABCC6, ABCC8, ABCD1, ABCD4, ABHD12, ABHD5, ACACA, ACAD9, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACE, ACKR1, ACO2, ACOX1, ACSF3, ACSL4, ACTA1, ACTA2, ACTB, ACTG1, ACVRL1, ACY1, ADAM10, ADAR, ADCY5, ADGRG1, ADGRV1, ADK, ADNP, ADSL, AFF2, AFG3L2, AGA, AGK, AGL, AGRN, AGXT, AHCY, AHI1, AIFM1, AIMP1, AKT1, AKT3, ALAD, ALDH18A1, ALDH3A2, ALDH4A1, ALDH5A1, ALDH7A1, ALDOA, ALDOB, ALG1, ALG11, ALG12, ALG13, ALG2, ALG3, ALG6, ALG8, ALG9, ALMS1, ALOX5AP, ALS2, ALX1, ALX3, ALX4, AMACR, AMN, AMPD1, AMPD2, AMT, ANG, ANK3, ANKRD11, ANO10, ANO3, ANO5, AP1S1, AP1S2, AP3B1, AP4B1, AP4E1, AP4M1, AP4S1, AP5Z1, APOA1, APOE, APP, APTX, AR, ARFGEF2, ARG1, ARHGAP31, ARHGEF10, ARHGEF6, ARHGEF9, ARID1A, ARID1B, ARL13B, ARL6, ARSA, ARSB, ARSE, ARSI, ARX, ASAH1, ASCL1, ASL, ASNS, ASPA, ASPM, ASS1, ASXL1, ASXL3, ATCAY, ATIC, ATL1, ATM, ATP13A2, ATP1A2, ATP1A3, ATP2A1, ATP2A2, ATP2B3, ATP2B4, ATP5E, ATP6AP2, ATP6V0A2, ATP7A, ATP7B, ATP8A2, ATPAF2, ATR, ATRX, ATXN3, B3GLCT, B4GALNT1, B4GALT1, B9D1, B9D2, BAG3, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BCAP31, BCKDHA, BCKDHB, BCKDK, BCOR, BCS1L, BDNF, BEST1, BICD2, BIN1, BLOC1S3, BLOC1S6, BOLA3, BRAF, BRAT1, BRWD3, BSCL2, BSND, C10orf2, C12orf57, C12orf65, C19orf12, C5orf42, C9orf72, CA8, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1H, CACNA1S, CACNB4, CACNG2, CAMTA1, CAPN3, CASC5, CASK, CASR, CAV3, CBL, CC2D1A, CC2D2A, CCDC28B, CCDC78, CCDC88C, CCM2, CCT5, CD207, CD320, CD36, CD59, CD96, CDH15, CDK11A, CDK5RAP2, CDKL5, CDON, CENPJ, CEP135, CEP152, CEP290, CEP41, CEP63, CERS1, CFL2, CHAT, CHCHD10, CHD2, CHD7, CHD8, CHMP1A, CHMP2B, CHRM3, CHRNA1, CHRNA2, CHRNA4, CHRNB1, CHRNB2, CHRND, CHRNE, CHRNG, CHSY1, CISD2, CISH, CIZ1, CLCN1, CLCN2, CLCNKA, CLCNKB, CLIC2, CLN3, CLN5, CLN6, CLN8, CNBP, CNTN1, CNTNAP2, CNTNAP4, COA5, COASY, COG1, COG4, COG5, COG6, COG7, COG8, COL12A1, COL18A1, COL4A1, COL4A2, COL6A1, COL6A2, COL6A3, COL7A1, COLQ, COQ2, COQ8A, COQ9, COX10, COX15, COX6A1, COX6B1, CP, CPA6, CPT2, CR1, CRADD, CRBN, CREBBP, CRYAB, CSF1R, CSF2RB, CSPP1, CST3, CSTB, CTC1, CTDP1, CTNNB1, CTSD, CUL4B, CWF19L1, CYP11B2, CYP27A1, CYP2U1, CYP7B1, DAG1, DARS2, DBT, DCAF17, DCTN1, DCX, DDHD1, DDHD2, DDOST, DEPDC5, DES, DGUOK, DHCR7, DHH, DHTKD1, DIAPH3, DKC1, DLD, DLG3, DMD, DNAH9, DNAJB2, DNAJB6, DNAJC19, DNAJC5, DNAJC6, DNM1L, DNM2, DNMT1, DOCK8, DOK7, DOLK, DPAGT1, DPM1, DPM3, DRD3, DSC3, DST, DTNBP1, DYNC1H1, DYNC2H1, DYRK1A, DYSF, EARS2, EBP, EDN3, EDNRB, EEF2, EFHC1, EFTUD2, EGR2, EHMT1, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF4E, EIF4G1, ELK1, ELOVL4, ELOVL5, EMD, EMX2, ENO3, ENTPD1, EOMES, EP300, EPB41L1, EPM2A, ERBB4, ERCC1, ERCC2, ERCC5, ERCC6, ERLIN1, ERLIN2, ESCO2, ETFA, ETFB, ETFDH, ETHE1, EXOC8, EXOSC3, EXOSC8, F2, F5, FA2H, FADD, FAM126A, FAM134B, FANCB, FASTKD2, FBLN5, FBXO38, FBXO7, FCGR2B, FGA, FGD1, FGD4, FGF10, FGF14, FGFR1, FGFR2, FGFR3, FH, FHL1, FIG4, FKRP, FKTN, FLNA, FLNC, FLRT1, FLVCR1, FLVCR2, FMR1, FOLR1, FOXG1, FOXP1, FOXP2, FOXP3, FOXRED1, FREM1, FRG1, FRMD7, FTL, FTO, FTSJ1, FUS, FXN, FZD9, GAA, GABRA1, GABRB3, GABRD, GABRG2, GAD1, GALC, GALNS, GAMT, GAN, GARS, GATM, GBA, GBA2, GBE1, GCDH, GCH1, GCSH, GDAP1, GDI1, GDNF, GFAP, GFER, GFM1, GFPT1, GIGYF2, GJB1, GJB3, GJC2, GK, GLB1, GLDC, GLI2, GLI3, GLRA1, GLRB, GM2A, GMPPB, GNAL, GNB4, GNE, GNPAT, GNS, GOSR2, GP1BA, GPC3, GPR143, GRIA3, GRID2, GRIK2, GRIN1, GRIN2A, GRIN2B, GRIP1, GRM1, GRN, GSN, GUSB, GYG1, GYS1, HADHA, HADHB, HCCS, HDAC4, HDAC8, HEPACAM, HERC2, HESX1, HEXA, HEXB, HFE, HGSNAT, HINT1, HK1, HMGCS2, HNRNPDL, HOXA1, HOXD10, HPCA, HPD, HPRT1, HPS1, HPS3, HPS4, HPS5, HPS6, HPSE2, HRAS, HSD17B10, HSD17B4, HSPB1, HSPB3, HSPB8, HSPD1, HTRA1, HTRA2, HTT, HUWE1, HYAL1, ICAM1, ICK, IDS, IDUA, IER3IP1, IFRD1, IFT140, IFT27, IGBP1, IGF1, IGHMBP2, IKBKAP, IKBKG, IL11RA, IL1RAPL1, IL1RN, INF2, INPP5E, INS, IQSEC2, IRX5, ISPD, ITM2B, ITPR1, JRK, KANK1, KARS, KAT6B, KBTBD13, KCNA1, KCNC3, KCND3, KCNE1L, KCNJ1, KCNJ10, KCNJ11, KCNK18, KCNK9, KCNMA1, KCNQ2, KCNQ3, KCNT1, KCTD7, KDM5C, KDM6A, KIAA0196, KIAA2022, KIF11, KIF1A, KIF1B, KIF1C, KIF21A, KIF5A, KIF7, KIRREL3, KLF8, KMT2A, KMT2D, KRAS, KRIT1, KRT5, L1CAM, LAMA2, LAMB1, LAMB2, LAMC3, AllNeuro panel LAMP2, LARGE, LBR, LDB3, LDHA, LGI1, LHX4, LIMS2, LINS, LITAF, LMBRD1, LMNA, LMNB1, LPIN1, LPIN2, LRP2, 5262 7, 8 LRPPRC, LRRK2, LRSAM1, LYZ, LZTFL1, MAG, MAGEL2, MAGI2, MAGT1, MAMLD1, MAN1B1, MAOA, MAPK10, MAPT, MARS, MARS2, MASP1, MATR3, MBD5, MBTPS2, MCEE, MCPH1, MECP2, MED12, MED17, MED23, MED25, MEF2C, MET, MFN2, MFSD8, MGAT2, MID1, MKKS, MKS1, MLC1, MMAA, MMAB, MMACHC, MMADHC, MOGS, MPDU1, MPDZ, MPI, MPV17, MPZ, MRE11A, MSX1, MSX2, MTFMT, MTHFR, MTM1, MTMR14, MTMR2, MTO1, MTOR, MTPAP, MTR, MTRR, MUSK, MUT, MVK, MYCN, MYF6, MYH14, MYH7, MYH9, MYO5A, MYOT, NAA10, NAGA, NAGLU, NAT8L, NBN, NDE1, NDP, NDRG1, NDST1, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA2, NDUFA4, NDUFA9, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFB3, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NEB, NEDD4L, NEFH, NEFL, NEU1, NF1, NFIX, NFU1, NGF, NHEJ1, NHLRC1, NHS, NIPA1, NIPBL, NKX2-1, NLGN3, NLGN4X, NLRP12, NLRP3, NOD2, NOG, NOL3, NOP56, NOS2, NOS3, NOTCH2, NOTCH3, NPC1, NPC2, NPHP1, NPHP3, NRAS, NRG1, NRXN1, NSD1, NSDHL, NSUN2, NT5C2, NTRK1, NTRK2, NUBPL, NXF5, OCLN, OCRL, OFD1, OPA1, OPA3, OPHN1, OPTN, ORC1, OTC, PAFAH1B1, PAH, PAK3, PANK2, PARK2, PARK7, PAX6, PC, PCBD1, PCDH19, PCK2, PCNT, PDCD10, PDE6D, PDE8B, PDHA1, PDK3, PDSS1, PDSS2, PDYN, PEX1, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6, PEX7, PFKM, PFN1, PGAM2, PGAP1, PGK1, PGM1, PHF6, PHF8, PHKA1, PHOX2B, PHYH, PIEZO2, PIGA, PIGL, PIGN, PIGO, PIGV, PIK3CA, PIK3R2, PIK3R5, PINK1, PLA2G6, PLCB1, PLEC, PLEKHG4, PLEKHG5, PLP1, PMM2, PMP22, PNKD, PNKP, PNPLA2, PNPLA6, PNPO, POGZ, POLG, POLG2, POLR3A, POLR3B, POMGNT1, POMGNT2, POMK, POMT1, POMT2, PORCN, PPT1, PQBP1, PREPL, PRICKLE1, PRICKLE2, PRKAG2, PRKCG, PRKCH, PRKRA, PRNP, PROP1, PRPH2, PRPS1, PRRT2, PRRX1, PRSS12, PRX, PSAP, PSEN1, PSEN2, PTCH1, PTEN, PTF1A, PTPN11, PTS, PUS1, PVRL1, PYGM, QARS, QDPR, RAB18, RAB39B, RAB3GAP1, RAB3GAP2, RAB40AL, RAB7A, RABGGTA, RAD21, RAD50, RAF1, RAI1, RANBP2, RAPSN, RARS2, RBBP8, RBFOX1, RBFOX3, RBM10, RBM8A, REEP1, REEP2, RELN, RET, RFT1, RIN2, RNASEH2A, RNASEH2B, RNASEH2C, RNASET2, RNF135, RNF170, RNU4ATAC, ROGDI, ROR2, RPGRIP1L, RPL10, RPS6KA3, RRM2B, RTN2, RUBCN, RYR1, SACS, SAMHD1, SBF1, SBF2, SCARB2, SCN10A, SCN1A, SCN1B, SCN2A, SCN3A, SCN4A, SCN5A, SCN8A, SCN9A, SCO1, SCO2, SCP2, SDCCAG8, SDHA, SDHAF1, SEPN1, SEPSECS, SERPINI1, SETBP1, SETD2, SETX, SGCA, SGCB, SGCD, SGCE, SGCG, SGSH, SH3TC2, SHANK2, SHANK3, SHH, SHOC2, SHROOM4, SIGMAR1, SIL1, SIX3, SIX6, SKI, SLC12A6, SLC13A5, SLC16A2, SLC17A5, SLC19A3, SLC1A3, SLC20A2, SLC22A5, SLC25A12, SLC25A19, SLC25A20, SLC25A22, SLC25A3, SLC25A4, SLC2A1, SLC30A10, SLC33A1, SLC35A1, SLC35A2, SLC35C1, SLC3A1, SLC4A1, SLC4A4, SLC5A7, SLC6A1, SLC6A3, SLC6A5, SLC6A8, SLC9A6, SLC9A9, SMARCA2, SMARCA4, SMARCB1, SMC1A, SMC3, SMCHD1, SMN1, SMN2, SMPD1, SMS, SNAP29, SNCA, SNCAIP, SNCB, SNIP1, SNX3, SOBP, SOD1, SORL1, SOS1, SOX10, SOX3, SPAST, SPG11, SPG20, SPG21, SPG7, SPR, SPTAN1, SPTBN2, SPTLC1, SPTLC2, SRD5A3, SRPX2, ST3GAL3, ST3GAL5, STIL, STRADA, STUB1, STXBP1, SUCLA2, SUCLG1, SUMF1, SURF1, SYN1, SYNE1, SYNE2, SYNGAP1, SYNJ1, SYP, SYT14, SZT2, TACO1, TAF1, TAF2, TARDBP, TAS2R38, TAZ, TBC1D24, TBCE, TBL1XR1, TBX1, TCAP, TCF4, TCTN1, TCTN2, TCTN3, TDP1, TECPR2, TECR, TFAP2A, TFAP2B, TFG, TG, TGFB1, TGFB2, TGFBR1, TGFBR2, TGIF1, TGM6, TH, THAP1, TICAM1, TIMM8A, TIRAP, TK2, TLR3, TLR5, TMCO1, TMEM126A, TMEM138, TMEM165, TMEM216, TMEM231, TMEM237, TMEM67, TMEM70, TMLHE, TNF, TNFSF4, TNNT1, TNPO3, TOR1A, TP63, TPK1, TPM2, TPM3, TPP1, TRAF3, TRAPPC11, TRAPPC9, TREM2, TREX1, TRIM2, TRIM32, TRPM6, TRPM7, TRPS1, TRPV4, TSC1, TSC2, TSEN2, TSEN34, TSEN54, TSFM, TSHB, TSHR, TSPAN7, TTBK2, TTC19, TTC21B, TTC8, TTI2, TTN, TTPA, TTR, TUBA1A, TUBA4A, TUBA8, TUBB2B, TUBB3, TUBB4A, TUBGCP6, TUSC3, TWIST1, TYMP, TYROBP, UBA1, UBE2A, UBE3A, UBQLN2, UCHL1, UMPS, UNC93B1, UPB1, UPF3B, UQCRB, UQCRQ, USP8, USP9X, VAMP1, VANGL1, VAPB, VAX1, VCP, VDAC1, VEGFA, VHL, VIPAS39, VLDLR, VPS13A, VPS13B, VPS35, VPS37A, VRK1, WAC, WDPCP, WDR45, WDR48, WDR62, WDR81, WFS1, WNK1, WNT10A, WNT3, WNT5A, WNT7A, WWOX, XBP1, XK, YAP1, YARS, YWHAE, ZBTB16, ZBTB18, ZCCHC12, ZDHHC15, ZDHHC9, ZEB2, ZFR, ZFYVE26, ZFYVE27, ZIC2, ZIC3, ZNF335, ZNF423, ZNF592, ZNF711, ZNF81

Test x Disease Gene OMIM Gene Available test methods code 46,XY gonadal dysgenesis, partial, with minifascicular neuropathy DHH 531 605423 2, 3, 4, 10, 11 Achalasia addisonianism alacrimia syndrome AAAS 121 605378 2, 3, 4, 7, 8, 10, 11 Acrocallosal syndrome KIF7 151 611254 2, 3, 4, 7, 8, 10, 11 Acyl-CoA peroxisomal oxidase deficiency ACOX1 615 609751 2, 4 Adrenoleukodystrophy, x-linked ABCD1 4 300371 2, 4, 7, 8, 10, 11 Adrenoleukodystrophy, x-linked PLXNB3 2214 300214 2, 4 Adrenoleukodystrophy/Adrenomyeloneuropathy ABCD1 4 300371 2, 4, 7, 8, 10, 11 Agenesis of the corpus callosum with peripheral neuropathy SLC12A6 267 604878 2, 3, 4, 7, 8, 10, 11 Aicardi-Goutieres syndrome type 1 TREX1 616 606609 2, 4, 10, 11 Aicardi-Goutieres syndrome type 2 RNASEH2B 617 610326 2, 4, 10, 11 Aicardi-Goutieres syndrome type 3 RNASEH2C 618 610330 2, 4, 10, 11 Aicardi-Goutieres syndrome type 4 RNASEH2A 619 606034 2, 4, 10, 11 Aicardi-Goutieres syndrome type 5 SAMHD1 620 606754 2, 4, 7, 8, 10, 11 Aicardi-Goutieres syndrome type 6 ADAR 86 146920 2, 4, 7, 8 Aicardi-Goutieres syndrome type 7 IFIH1 2188 606951 2, 4, 7, 8 Alexander disease GFAP 621 137780 2, 3, 4, 10, 11 Allan-Herndon-Dudley syndrome SLC16A2 268 300095 2, 3, 4, 10, 11 Allan-Herndon-Dudley syndrome SLC16A2 268 300095 2, 3, 4, 10, 11 Alpha-thalassemia/mental retardation syndrome ATRX 27 300032 2, 4, 7, 8, 10, 11 Al-Raqad syndrome DCPS 2742 610534 2, 4 Alternating hemiplegia of childhood type 1 ATP1A2 587 182340 2, 4, 7, 8, 10, 11 Alternating hemiplegia of childhood type 2 ATP1A3 560 182350 2, 4, 7, 8, 10, 11 Alzheimer disease type 1 APP 761 104760 2, 4, 7, 8, 10, 11 Alzheimer disease type 2 APOE 18 107741 2, 3, 4, 10, 11 Alzheimer disease type 3 PSEN1 233 104311 2, 4, 7, 8, 10, 11 Alzheimer disease type 4 PSEN2 234 600759 2, 4, 10, 11 Alzheimers disease, early onset, autosomal dominant SORL1 1286 602005 2, 3, 4, 7, 8, 10, 11 Alzheimers disease, RTN3 related RTN3 2354 604249 2, 4 Amish infantile epilepsy syndrome ST3GAL5 764 604402 2, 4 Amyloidosis TTR 542 176300 2, 3, 4, 10, 11 Amyloidosis, finnish type GSN 1958 137350 2, 4, 7, 8 Amyotrophic lateral sclerosis risk factor CHGB 645 118920 2, 4 Amyotrophic lateral sclerosis type 1 SOD1 691 147450 2, 3, 4, 10, 11 Amyotrophic lateral sclerosis type 2, juvenile ALS2 692 606352 2, 3, 4, 7, 8, 10, 11 Amyotrophic lateral sclerosis type 4 SETX 264 608465 2, 4, 7, 8, 10, 11 Amyotrophic lateral sclerosis type 6 FUS 38 137070 2, 3, 4, 7, 8, 10, 11 Amyotrophic lateral sclerosis type 8 VAPB 693 605704 2, 4 Amyotrophic lateral sclerosis type 9 ANG 694 105850 2, 4 Amyotrophic lateral sclerosis type 10 TARDBP 287 605078 2, 3, 4, 10, 11 Amyotrophic lateral sclerosis type 11 FIG4 530 609390 2, 3, 4, 7, 8, 10, 11 Amyotrophic lateral sclerosis type 12 OPTN 205 602432 2, 3, 4, 7, 8, 10, 11 Amyotrophic lateral sclerosis type 14 VCP 1594 601023 2, 4, 7, 8 Amyotrophic lateral sclerosis type 16 SIGMAR1 1624 601978 2, 4 Amyotrophic lateral sclerosis type 17 CHMP2B 1623 609512 2, 4 Amyotrophic lateral sclerosis type 18 PFN1 93 176610 2, 4 Amyotrophic lateral sclerosis type 21 MATR3 737 164015 2, 3, 4, 7, 8, 10, 11 Amyotrophic lateral sclerosis with frontotemporal dementia C9orf72 1241 614260 12 Amyotrophic lateral sclerosis, CREST related SS18L1 1614 606472 2, 4 Amyotrophic lateral sclerosis, susceptibility to NEFH 1595 162230 2, 3, 4, 7, 8, 10, 11 Amyotrophic lateral sclerosis, VPS54 related VPS54 1625 614633 2, 4, 7, 8 Amyotrophic lateral sclerosis, x-linked juvenile and adult-onset ALS UBQLN2 696 300264 2, 4 Amyotrophy hereditary neuralgic SEPT9 543 604061 2, 4, 7, 8, 10, 11 Angelman syndrome chr. 15q11 91 10 Angelman syndrome UBE3A 312 601623 2, 4, 7, 8, 10, 11 Angelman-like syndrome CDKL5 770 300203 2, 4, 7, 8, 10, 11 Angelman-like syndrome MECP2 163 300005 2, 4, 10, 11 Arts syndrome PRPS1 231 311850 2, 3, 4, 10, 11 Asperger syndrome susceptibility X-linked type 2 NLGN3 186 300336 2, 3, 4, 10, 11 Ataxia and muscle hypotonia COX20 1794 614698 2, 4 Ataxia telangiectasia like disorder MRE11A 1151 600814 2, 3, 4, 7, 8, 10, 11 Ataxia, posterior column, with retinitis pigmentosa FLVCR1 1590 609144 2, 3, 4, 7, 8, 10, 11 Ataxia, progressive seizures, mental deterioration, and hearing loss, MT-TV related MT-TV 2555 590105 4

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code ATF6, CNGA3, CNGB3, CNNM4, GNAT2, OPN- Achromatopsia panel RPGR 5354 5, 6, 7, 8, 9, 10 1LW, OPN1MW, PDE6C, PDE6H, RPGR AP3B1, BLOC1S3, BLOC1S6, C10ORF11, DTNBP1, EDN3, EDNRB, GPR143, HPS1, HPS3, EDNRB, PAX3, EDN3, SNAI2, Albinism panel HPS4, HPS5, HPS6, KIT, LYST, MC1R, MITF, SOX10, KIT, OCA2, GPR143, TYR, 5000 5, 6, 7, 8, 9, 10 MLPH, MYO5A, OCA2, PAX3, RAB27A, SL- MITF C24A5, SLC45A2, SNAI2, SOX10, TYR, TYRP1 AGK, BCOR, BFSP1, BFSP2, CHMP4B, CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGB, CRYGC, CRYGD, CRYGS, CTDP1, EPHA2, EYA1, FOXC1, FOXE3, Cataract panel WFS1, PAX6, EYA1, FOXC1 5006 5, 6, 7, 8, 9, 10 FTL, FYCO1, GALK1, GCNT2, GJA3, GJA8, HSF4, LEMD2, LIM2, LSS, MAF, MIP, NHS, P3H2, PAX6, PITX3, SIPA1L3, SLC16A12, TDRD7, UNC45B, VIM, VSX2, WFS1 Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes ABCA4, ADAM9, AIPL1, BEST1, C8ORF37, CABP4, CACNA1F, CACNA2D4, CDHR1, CER- KL, CNGB3, CNNM4, CRX, GUCA1A, GUCY2D, PRPH2, GUCY2D, CRX, RPGR, Cone-rod and cone dystrophy panel 5045 5, 6, 7, 8, 9, 10 KCNV2, PDE6C, PDE6H, PITPNM3, PROM1, BEST1, ABCA4, RPGRIP1, AIPL1 PRPH2, RAX2, RDH5, RGS9, RGS9BP, RIMS1, RPGR, RPGRIP1, SEMA4A, UNC119 CHM, EFEMP1, PLA2G5, RDH5, RLBP1, RS1, Flecked retina panel CHM, VPS13B 5059 5, 6, 7, 8, 9, 10 VPS13B ACVR1, ASB10, BEST1, CANT1, COL18A1, CYP1B1, FOXC1, LMX1B, LOXL1, LTBP2, SBF2, PITX2, PAX6, LMX1B, Glaucoma panel 5270 5, 6, 7, 8, 9, 10 MYOC, NTF4, OPTN, PAX6, PITX2, PITX3, BEST1, FOXC1, CYP1B1 SBF2, WDR36 HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, Hermansky-Pudlak syndrome panel 5047 5, 6, 7, 8, 9 DTNBP1, BLOC1S3 AIPL1, CABP4, CEP290, CRB1, CRX, GUCY2D, RPE65, GUCY2D, CRX, RPGRIP1, IMPDH1, IQCB1, KCNJ13, LCA5, LRAT, NM- Leber congenital amaurosis panel IMPDH1, CEP290, LCA5, RDH12, 5039 5, 6, 7, 8, 9, 10 NAT1, OTX2, RD3, RDH12, RPE65, RPGRIP1, AIPL1, CRB1 SPATA7, TULP1 MT-ATP6, MT-CO1, MT-CO3, MT-CYB, MT- Leber optic atrophy panel ND1, MT-ND2, MT-ND4, MT-ND4L, MT-ND5, 5112 7 MT-ND6 ABCB6, ALDH1A3, BCOR, BMP4, CHD7, ERCC1, ERCC2, ERCC5, ERCC6, FOXE3, FOXL2, FRAS1, FREM1, FREM2, GDF3, GDF6, GJA1, GRIP1, HCCS, HMGB3, HMX1, MAB21L2, Microphthalmia/anophthalmia/coloboma SHH, SIX3, NDP, PAX6, FOXL2, MFRP, NAA10, NDP, OCRL, OTX2, PAX2, PAX6, 5327 5, 6, 7, 8, 9, 10 spectrum panel CHD7, BMP4, SOX2 PRSS56, RAB18, RAB3GAP1, RAB3GAP2, RARB, RAX, RBP4, SALL2, SHH, SIX3, SIX6, SMOC1, SOX2, STRA6, TBC1D20, TENM3, TFAP2A, VAX1, VSX2 Oculomotor apraxia panel APTX, PIK3R5, PNKP, SETX SETX, APTX 5055 5, 6, 7, 8, 9, 10 Ophthalmoplegia (progressive external) DGUOK, DNA2, OPA1, POLG, POLG2, RRM2B, TWNK, POLG2, RRM2B, POLG, 5043 5, 6, 7, 8, 9, 10 panel SLC25A4, TK2, TWNK, TYMP OPA1, SLC25A4, DGUOK, TK2 ACO2, AFG3L2, C12ORF65, CISD2, MFN2, Optic atrophy panel NR2F1, OPA1, OPA3, RTN4IP1, SLC25A46, WFS1, SPG7, OPA1, MFN2 5044 5, 6, 7, 8, 9, 10 SPG7, TIMM8A, TMEM126A, WFS1 ABCA4, BEST1, CA4, CRX, CLRN1, FSCN2, GU- CA1B, IMPDH1, KLHL7, NR2E3, NRL, PRPF3, PRPH2, RPE65, PRPF31, CRX, Retinitis pigmentosa panel, autosomal PRPF31, PRPF6, PRPF8, PRPH2, RDH12, RGR, RPGR, RP2, RDH12, RHO, BEST1, 5023 5, 6, 7, 8, 9, 10 dominant RHO, ROM1, RP1, RP2, RP9, RPE65, RPGR, ABCA4, IMPDH1, RP1 SEMA4A, SNRNP200, TOPORS ABCA4, ARL6, BBS1, BEST1, C2ORF71, C8ORF37, CERKL, CNGA1, CNGB1, CRB1, DHDDS, EYS, FAM161A, FLVCR1, GNPTG, EYS, RPE65, RPGR, RP2, RDH12, Retinitis pigmentosa panel, autosomal IDH3B, IMPG2, LRAT, MAK, MERTK, NR2E3, RHO, BEST1, ABCA4, USH2A, 5032 5, 6, 7, 8, 9, 10 recessive NRL, PDE6A, PDE6B, PDE6G, PRCD, PROM1, RP1, CRB1 RBP3, RDH12, RGR, RHO, RLBP1, RP1, RP2, RPE65, RPGR, SAG, SEMA4A, SPATA7, TTC8, TULP1, USH2A, ZNF513 ABCA4, BEST1, C1QTNF5, CDH3, CNGB3, BEST1, ABCA4, RPGR, RDH12, Stargardt disease panel ELOVL4, FSCN2, PROM1, PRPH2, RDH12, 5093 5, 6, 7, 8, 9, 10 PRPH2 RP1L1, RPGR, TIMP3 COL2A1, COL9A1, COL9A2, COL11A1, Stickler syndrome panel COL2A1, COL11A1 5031 5, 6, 7, 8, 9, 10 COL11A2 ADGRV1, CDH23, CIB2, CLRN1, MYO7A, Usher syndrome panel USH2A, PCDH15 5218 5, 6, 7, 8, 9, 10 PCDH15, PDZD7, USH1C, USH1G, USH2A

› Ophthalmological Diseases

Test x Disease Gene OMIM Gene Available test methods code Achromatopsia type 2 CNGA3 50 600053 2, 4, 7, 8 Achromatopsia type 3 CNGB3 940 605080 1, 2, 3, 4, 7, 8, 10, 11 Achromatopsia type 4 GNAT2 51 139340 2, 4 Achromatopsia type 6 PDE6H 1604 601190 2, 4 Aland Island eye disease CACNA1F 861 300110 2, 4, 7, 8 Albinism, ocular type I, Nettleship-Falls type GPR143 131 300808 2, 4, 10, 11 Albinism, oculocutaneous nonsyndromic SLC24A5 1631 609802 2, 4 Albinism, oculocutaneous type 1A TYR 311 606933 2, 4, 10, 11 Albinism, oculocutaneous type 1B TYR 311 606933 2, 4, 10, 11 Albinism, oculocutaneous type 2 OCA2 991 611409 2, 4, 7, 8, 10, 11 Albinism, oculocutaneous type 3 TYRP1 862 115501 2, 3, 4, 10, 11 Albinism, oculocutaneous type 4 SLC45A2 863 606202 2, 3, 4, 10, 11 Albinism, oculocutaneous type 5 C10ORF11 1538 614537 2, 4 Alstrom syndrome ALMS1 864 606844 2, 3, 4, 7, 8, 10, 11 Aniridia PAX6 207 607108 2, 4, 7, 8, 10, 11 Anterior segment mesenchymal dysgenesis PITX3 2571 602669 2, 4 Bardet-Biedl syndrome type 14 CEP290 642 610142 2, 3, 4, 10, 11 Bestrophinopathy BEST1 865 607854 2, 4, 10, 11 Bietti crystalline corneoretinal dystrophy CYP4V2 2901 608614 2, 4, 10, 11 Blepharophimosis, epicanthus inversus, and ptosis FOXL2 1516 605597 2, 4, 10, 11 Blepharophimosis-ptosis-intellectual disability syndrome UBE3B 1907 608047 2, 4, 7, 8 Bothnia retinal dystrophy RLBP1 866 180090 2, 3, 4, 10, 11 Bradyopsia RGS9 1605 604067 2, 4, 7, 8 Bradyopsia RGS9BP 1606 607814 2, 4 Branchiootorenal syndrome type 1 EYA1 125 601653 2, 4, 7, 8, 10, 11 Branchiootorenal syndrome type 2 SIX5 2060 600963 2, 3, 4, 10, 11 Brittle cornea syndrome ZNF469 867 612078 2, 4, 7, 8 Cataract 11, multiple types PITX3 2571 602669 2, 4 Cataract type 17, multiple types CRYBB1 873 600929 2, 4 Cataract type 23 CRYBA4 2000 123631 2, 4 Cataract type 41 WFS1 325 606201 2, 4, 10, 11 Cataract type 43 UNC45B 2774 611220 2, 4, 7, 8 Cataract, autosomal dominant GCNT2 868 600429 2, 4, 7, 8 Cataract, autosomal recessive congenital nuclear type 2 CRYBB3 872 123630 2, 4 Cataract, autosomal recessive congenital type 1 CRYAA 869 123580 2, 4 Cataract, autosomal recessive congenital type 2 FYCO1 870 607182 2, 4, 7, 8 Cataract, autosomal recessive congenital type 4 TDRD7 871 611258 2, 4, 7, 8 Cataract, autosomal recessive type 38 AGK 1092 610345 2, 3, 4, 7, 8, 10, 11 Cataract, congenital SORD 2526 182500 2, 4 Cataract, congenital, associated with Marinesco-Sjogren Syndrome SIL1 874 608005 2, 3, 4, 10, 11 Cataract, cortical pulverulent, late-onset LIM2 875 154045 2, 4 Cataract, lamellar HSF4 876 602438 2, 4, 7, 8 Cataract, posterior polar type 2 CRYAB 690 123590 2, 4 Cataract, pulverulent or cerulean, with or without microcornea MAF 2222 177075 2, 4, 10, 11 Cataract, X-linked NHS 185 300457 2, 3, 4, 7, 8, 10, 11 Cataract-microcornea syndrome GJA8 877 600897 2, 4, 10, 11 Cerebellar-retinal degeneration, infantile ACO2 2898 100850 2, 4, 7, 8 Choroidal dystrophy, central areolar type 2 PRPH2 230 179605 2, 4, 10, 11 Coat plus syndrome CTC1 1288 613129 2, 3, 4, 7, 8, 10, 11 Coloboma of optic nerve PAX6 207 607108 2, 4, 7, 8, 10, 11 Coloboma, ocular, autosomal dominant PAX6 207 607108 2, 4, 7, 8, 10, 11 Colobomatous microphthalmia TENM1 522 610083 2, 3, 4, 7, 8, 10, 11 Cone-rod dystrophy AIPL1 1349 604392 2, 4, 10, 11 Cone-rod dystrophy UNC119 1442 604011 2, 4 Cone-rod dystrophy type 2 CRX 1364 602225 2, 4, 10, 11 Cone-rod dystrophy type 3 ABCA4 2 601691 2, 4, 7, 8, 10, 11 Cone-rod dystrophy type 4 PDE6C 1398 600827 2, 4, 7, 8

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code Alport syndrome panel COL4A3, COL4A4, COL4A5 COL4A4, COL4A5, COL4A3 5034 5, 6, 7, 8, 9, 10 Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes ARMC4, C21orf59, CCDC103, CCDC114, CCDC151, CCDC39, CCDC40, CCDC65, CCNO, DNAAF1, DNAAF2, DNAAF3, DNAAF4, Ciliary (primary) dyskinesia panel DNAI1, DNAH5 5075 5, 6, 7, 8, 9, 10 DNAAF5, DNAH11, DNAH5, DNAI1, DNAI2, DNAL1, DRC1, HYDIN, LRRC6, NME8, RSPH1, RSPH4A, RSPH9, SPAG1, ZMYND10 ACTG1, CCDC50, COCH, COL11A2, CRYM, DFNA5, DIABLO, DIAPH1, DIAPH3, EYA4, Deafness, non-syndromic sensorineural GJB2, GJB3, GJB6, GRHL2, KCNQ4, MIR96, WFS1, GJB6, GJB3, POU3F4, 5010 5, 6, 7, 8, 9, 10 autosomal dominant panel MYH14, MYH9, MYO6, MYO7A, POU3F4, MYH9, GJB2 POU4F3, PRPS1, SIX1, SLC17A8, SMPX, TECTA, TJP2, TMC1, WFS1 CDH23, CLDN14, COL11A2, DFNB59, ESPN, ESRRB, FOXI1, GIPC3, GJB2, GJB3, GJB6, GPSM2, GRXCR1, HGF, ILDR1, KCNJ10, LHF- PL5, LOXHD1, LRTOMT, MARVELD2, MSRB3, Deafness, non-syndromic sensorineural PCDH15, GJB6, GJB3, POU3F4, MYO15A, MYO3A, MYO6, MYO7A, OTOA, 5011 5, 6, 7, 8, 9, 10 autosomal recessive panel SLC26A4, GJB2 OTOF, PCDH15, POU3F4, PRPS1, PTPRQ, RDX, SERPINB6, SLC12A1, SLC26A4, SLC26A5, SMPX, STRC, TECTA, TMC1, TMIE, TMPRSS3, TPRN, TRIOBP, USH1C

› Ear, Nose and Throat Diseases

Test x Disease Gene OMIM Gene Available test methods code Alport syndrome, autosomal recessive COL4A3 983 120070 2, 4, 7, 8, 10, 11 Alport syndrome, autosomal recessive COL4A4 984 120131 2, 4, 7, 8, 10, 11 Alport syndrome, X-Linked COL4A5 985 303630 2, 4, 7, 8, 10, 11 Auditory neuropathy, autosomal dominant DIAPH3 1674 614567 2, 4, 7, 8 Auriculocondylar syndrome type 2 PLCB4 1015 600810 2, 3, 4, 7, 8, 10, 11 Branchiootic syndrome type 1 EYA1 125 601653 2, 4, 7, 8, 10, 11 Brown-Vialetto-Van Laere syndrome 1 SLC52A3 1941 613350 2, 3, 4, 10, 11 Brown-Vialetto-Van Laere syndrome type 2 SLC52A2 3021 607882 2, 4 Ciliogenesis related disorder PTPN23 1973 606584 2, 4 Deafness and male infertility, CATSPER2 related CATSPER2 1233 607249 2, 4 Deafness with keratopachydermia and constrictions of fingers and toes GJB2 953 121011 2, 4, 10, 11 Deafness, autosomal dominant type 1 DIAPH1 965 602121 2, 4, 7, 8 Deafness, autosomal dominant type 2A KCNQ4 966 603537 2, 3, 4, 7, 8, 10, 11 Deafness, autosomal dominant type 2B GJB3 964 603324 2, 4, 10, 11 Deafness, autosomal dominant type 3A GJB2 953 121011 2, 4, 10, 11 Deafness, autosomal dominant type 3B GJB6 954 604418 2, 4, 10, 11 Deafness, autosomal dominant type 4 MYH14 970 608568 2, 4, 7, 8 Deafness, autosomal dominant type 4B CEACAM16 2443 614591 2, 4 Deafness, autosomal dominant type 5 DFNA5 971 608798 2, 4 Deafness, autosomal dominant type 6 WFS1 325 606201 2, 4, 10, 11 Deafness, autosomal dominant type 9 COCH 972 603196 2, 3, 4, 10, 11 Deafness, autosomal dominant type 10 EYA4 973 603550 2, 3, 4, 7, 8, 10, 11 Deafness, autosomal dominant type 11 MYO7A 178 276903 2, 3, 4, 7, 8, 10, 11 Deafness, autosomal dominant type 12 TECTA 974 602574 2, 4, 7, 8 Deafness, autosomal dominant type 13 COL11A2 945 120290 2, 4, 7, 8 Deafness, autosomal dominant type 15 POU4F3 224 602460 2, 4 Deafness, autosomal dominant type 17 MYH9 179 160775 2, 4, 7, 8, 10, 11 Deafness, autosomal dominant type 20 ACTG1 989 102560 2, 3, 4, 10, 11 Deafness, autosomal dominant type 22 MYO6 976 600970 2, 4, 7, 8 Deafness, autosomal dominant type 23 SIX1 977 601205 2, 4, 10, 11 Deafness, autosomal dominant type 25 SLC17A8 1665 607557 2, 4, 7, 8 Deafness, autosomal dominant type 28 GRHL2 1666 608576 2, 4, 7, 8 Deafness, autosomal dominant type 36 TMC1 300 606706 2, 3, 4, 7, 8, 10, 11 Deafness, autosomal dominant type 39, with dentinogenesis type 1 DSPP 1667 125485 2, 4

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code ALPL, ANKH, AP2S1, CASR, CLCN5, CYP27B1, Abnormal mineralization panel CYP2R1, DMP1, ENPP1, FGF23, GNA11, PHEX, PHEX, FGF23, CASR 5307 5, 6, 7, 8, 9, 10 PTH1R, SLC34A1, SLC34A3, SLC9A3R1, VDR Autoimmune lymphoproliferative syndro- CASP10, CASP8, CTLA4, FADD, FAS, FASLG, FAS, FASLG 5324 5, 6, 7, 8, 9, 10 me panel ITK, KRAS, MAGT1, NRAS, PRKCD Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes Chronic granulomatous disease panel CYBA, CYBB, NCF1, NCF2, NCF4 5283 5, 6, 7, 8 Common variable immune deficiency ICOS, NFKB2, TNFRSF13B, TNFRSF13C 5246 5, 6, 7, 8, 9 (CVID) panel ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, Congenital ichthyosis panel 5095 5, 6, 7, 8, 9 LIPN, NIPAL4, PNPLA1, TGM1 AFF4, HDAC8, KMT2A, NIPBL, RAD21, SMC1A, Cornelia de Lange syndrome panel NIPBL 5119 5, 6, 7, 8, 9, 10 SMC3, TAF6 ALDH18A1, ATP6V0A2, ATP7A, EFEMP2, ELN, Cutis laxa panel ATP7A, ELN 5260 5, 6, 7, 8, 9, 10 FBLN5, LTBP4, PYCR1 ADAMTS2, ATP7A, B3GALT6, B3GAT3, B4GALT7, CHST14, COL12A1, COL1A1, ELN, FBN1, COL1A1, FLNA, Ehlers-Danlos syndrome and related disor- COL1A2, COL3A1, COL5A1, COL5A2, DSE, TNXB, COL5A1, PLOD1, COL1A2, 5052 5, 6, 7, 8, 9, 10 ders panel EFEMP2, ELN, FBLN5, FBN1, FKBP14, FLNA, COL3A1, ATP7A GORAB, LTBP4, PLOD1, PRDM5, PYCR1, RIN2, SLC39A13, TNXB, ZNF469 CHST8, COL17A1, COL7A1, CSTA, DSG1, DSP, DST, EXPH5, FERMT1, ITGA3, ITGA6, ITGB4, Epidermolysis bullosa panel KRT5, JUP, DSP, COL7A1 5102 5, 6, 7, 8, 9, 10 JUP, KRT14, KRT5, LAMA3, LAMB3, LAMC2, MMP1, PKP1, PLEC, TGM5 BRCA2, BRIP1, ERCC4, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCD2, BRIP1, FANCB, PALB2, Fanconi anemia panel 5012 5, 6, 7, 8, 9, 10 FANCL, FANCM, PALB2, RAD51C, SLX4, BRCA2, FANCA, RAD51C UBE2T, XRCC2 Hemophagocytic Lymphohistiocytosis PRF1, UNC13D, STX11, STXBP2 UNC13D, STX11, PRF1 5212 5, 6, 7, 8, 9, 10 panel ABCA12, ALOX12B, ALOXE3, AP1S1, CERS3, CLDN1, CYP4F22, EBP, ERCC2, ERCC3, FLG, GJB2, GJB3, GJB4, GTF2H5, KRT1, KRT10, Ichthyosis extended panel GJB3, STS, GJB2 5273 5, 6, 7, 8, 9, 10 KRT2, LIPN, LOR, MPLKIP, NIPAL4, PEX7, PHYH, PNPLA1, POMP, SLC27A4, SNAP29, SPINK5, ST14, STS, SUMF1, TGM1, TGM5 Melanoma panel BAP1, CDK4, CDKN2A, MITF, TERT BAP1, CDKN2A, CDK4, MITF, TERT 5342 5, 6, 7, 8, 9, 10 Neurofibromatosis panel NF1, NF2, SMARCB1, SPRED1 SMARCB1, SPRED1, NF2, NF1 5209 5, 6, 7, 8, 10 APCDD1, CDSN, DSG4, HR, KRT71, KRT74, Nonsyndromic hypotrichosis panel 5290 5, 6, 7, 8, 9 LIPH, LPAR6, RPL21, SNRPE ALPL, BMP1, COL1A1, COL1A2, CREB3L1, Osteogenesis imperfecta and low bone CRTAP, FKBP10, IFITM5, P3H1, LRP5, PLOD2, PLS3, COL1A1, LRP5, COL1A2 5249 5, 6, 7, 8, 9, 10 density disorders panel PLS3, PPIB, SERPINF1, SERPINH1, SP7, TMEM38B, WNT1 ANKH, CA2, CLCN7, COL1A1, GJA1, HPGD, LRP5, MTAP, OSTM1, PLEKHM1, PTDSS1, Osteopetrosis and high bone density SLCO2A1, SNX10, SOST, TBXAS1, TCIRG1, COL1A1, LRP5, MTAP 5060 5, 6, 7, 8, 9, 10 disorders panel TGFB1, TNFRSF11A, TNFRSF11B, TNFSF11, TYROBP ELANE, LPIN2, MEFV, MVK, NLRP3, PSTPIP1, Periodic fever syndrome panel MEFV 5224 5, 6, 7, 8, 9, 10 TNFRSF1A ADA, AICDA, ATM, BLNK, BTK, CD19, CD40, CD40LG, CD79A, CD79B, CD81, CR2, DCL- RE1C, ICOS, IGHM, IGLL1, IKBKG, IL2RG, LRBA, XIAP, RAG2, SH2D1A, ATM, Primary antibody deficiency panel LRRC8A, MS4A1, NCF1, NFKB2, NFKBIA, PIK- 5317 5, 6, 7, 8, 10 PLCG2, DCLRE1C, BTK 3CD, PIK3R1, PLCG2, PRKDC, PTPRC, RAG1, RAG2, SH2D1A, TNFRSF13B, TNFRSF13C, UNG, XIAP Susceptibility to atypical mycobacterium CYBB, IFNGR1, IFNGR2, IKBKG, IL12A, IL12B, 5272 7, 8, 9 disease panel IL12RB1, IL12RB2, IRF8, ISG15, STAT1, TYK2 EDN3, MITF, EDNRB, SNAI2, Waardenburg syndrome panel EDN3, EDNRB, MITF, PAX3, SNAI2, SOX10, TYR 5221 5, 6, 7, 8, 9, 10 SOX10, PAX3, TYR

Test x Disease Gene OMIM Gene Available test methods code 3MC syndrome type 1 MASP1 1293 600521 2, 4, 7, 8 3MC syndrome type 2 COLEC11 1294 612502 2, 4 Achondrogenesis type 1A TRIP11 1928 604505 2, 3, 4, 7, 8, 10, 11 Achondrogenesis type 1B SLC26A2 1933 606718 2, 3, 4, 10, 11 Achondrogenesis type 2 COL2A1 943 120140 2, 4, 7, 8, 10, 11 Achondroplasia FGFR3 1452 134934 1, 2, 3, 4, 10, 11 Acne inversa familial type 3 PSEN1 233 104311 2, 4, 7, 8, 10, 11 Acrodermatitis enteropathica SLC39A4 1358 607059 2, 3, 4, 10, 11 Acrodysostosis 2 PDE4D 1053 600129 2, 3, 4, 7, 8, 10, 11 Acrofacial dysostosis 1, Nager type SF3B4 742 605593 2, 3, 4, 10, 11 Adams-Oliver syndrome type 1 ARHGAP31 990 610911 2, 3, 4, 7, 8, 10, 11 Adams-Oliver syndrome type 2 DOCK6 1275 614194 2, 3, 4, 7, 8, 10, 11 Adams-Oliver syndrome type 3 RBPJ 1799 147183 2, 4 Adams-Oliver syndrome type 4 EOGT 2633 614789 2, 3, 4, 7, 8, 10, 11 Albinism, oculocutaneous nonsyndromic SLC24A5 1631 609802 2, 4 Albinism, oculocutaneous type 1A TYR 311 606933 2, 4, 10, 11 Albinism, oculocutaneous type 1B TYR 311 606933 2, 4, 10, 11 Albinism, oculocutaneous type 2 OCA2 991 611409 2, 4, 7, 8, 10, 11 Albinism, oculocutaneous type 3 TYRP1 862 115501 2, 3, 4, 10, 11 Albinism, oculocutaneous type 4 SLC45A2 863 606202 2, 3, 4, 10, 11 Albinism, oculocutaneous type 5 C10ORF11 1538 614537 2, 4 Alopecia universalis HR 2692 602302 2, 3, 4, 7, 8, 10, 11 Amelogenesis imperfecta type 1A LAMB3 1025 150310 2, 3, 4, 10, 11 Amelogenesis imperfecta type 1B ENAM 2720 606585 2, 4, 7, 8 Amelogenesis imperfecta type 1C ENAM 2720 606585 2, 4, 7, 8 Amelogenesis imperfecta type 1E AMELX 2717 300391 2, 4 Amelogenesis imperfecta type 1F AMBN 2711 601259 2, 4 Amelogenesis imperfecta type 1G FAM20A 2719 611062 2, 4, 7, 8 Amelogenesis imperfecta type 1H ITGB6 2712 147558 2, 4, 7, 8 Amelogenesis imperfecta type 2A1 KLK4 2709 603767 2, 4 Amelogenesis imperfecta type 2A2 MMP20 2710 604629 2, 4 Amelogenesis imperfecta type 2A3 WDR72 2715 613214 2, 4, 7, 8 Amelogenesis imperfecta type 2A4 C4orf26 2713 614829 2, 4 Amelogenesis imperfecta type 2A5 SLC24A4 1526 609840 2, 4, 7, 8 Amelogenesis imperfecta type 3 FAM83H 2718 611927 2, 4 Amelogenesis imperfecta type 4 DLX3 1748 600525 2, 3, 4, 10, 11 Amelotin deficiency AMTN 2714 610912 2, 4 Amyloidosis, primary localized cutaneous, type 1 OSMR 2348 601743 2, 4, 7, 8 Amyloidosis, primary localized cutaneous, type 2 IL31RA 2349 609510 2, 4 Arthrogryposis, distal, type 1A TPM2 306 190990 2, 3, 4, 10, 11 Arthrogryposis, distal, type 1B MYBPC1 992 160794 2, 3, 4, 7, 8, 10, 11 Arthrogryposis, distal, type 2A MYH3 175 160720 2, 3, 4, 7, 8, 10, 11 Arthrogryposis, distal, type 2B MYH3 175 160720 2, 3, 4, 7, 8, 10, 11 Arthrogryposis, distal, type 2B TNNI2 994 191043 2, 4 Arthrogryposis, distal, type 2B TNNT3 993 600692 2, 4, 7, 8 Arthrogryposis, distal, type 3 PIEZO2 2397 613629 2, 3, 4, 7, 8, 10, 11 Arthrogryposis, distal, type 5 PIEZO2 2397 613629 2, 3, 4, 7, 8, 10, 11 Arthrogryposis, distal, type 5D ECEL1 2536 605896 2, 3, 4, 7, 8, 10, 11 Arthrogryposis, distal, type 7 MYH8 995 160741 2, 3, 4, 7, 8, 10, 11 Arthrogryposis, mental retardation, and seizures SLC35A3 1931 605632 2, 4 Arthrogryposis, renal dysfunction, and cholestasis type 1 VPS33B 1760 608552 2, 4, 7, 8 Arthrogryposis, renal dysfunction, and cholestasis type 2 VIPAS39 2467 613401 2, 3, 4, 7, 8, 10, 11 Arthropathy, progressive pseudorheumatoid, of childhood WISP3 326 603400 2, 4 Atelosteogenesis type 1 FLNB 1884 603381 2, 4, 7, 8, 10, 11 Atelosteogenesis type 3 FLNB 1884 603381 2, 4, 7, 8, 10, 11 Atrichia with papular lesions HR 2692 602302 2, 3, 4, 7, 8, 10, 11 Atypical Mycobacterial infection IFNGR2 1987 147569 2, 4 Atypical Mycobacterial infection IKBKG 1740 300248 2, 3, 4, 10, 11 Atypical Mycobacterial infection IL12RB1 1999 601604 2, 4, 7, 8 Atypical Mycobacterial infection STAT1 2076 600555 2, 4, 7, 8 Atypical Mycobacterial infection, IL12RB2 related IL12RB2 2105 601642 2, 4, 7, 8 Autoimmune lymphoproliferative syndrome type 1A FAS 1109 134637 2, 3, 4, 10, 11

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code AKAP9, ANK2, CACNA1C, CACNB2, CASQ2, CAV3, DSC2, DSG2, DSP, GPD1L, HCN4, JUP, DSG2, SCN5A, CAV3, PKP2, KCNA5, KCND3, KCNE1, KCNE2, KCNE3, KCNQ1, KCNE2, DSC2, RYR2, Arrhythmia, hereditary panel 5027 5, 6, 7, 8, 9, 10 KCNH2, KCNJ2, KCNQ1, NPPA, PKP2, PLN, KCNE1, KCNH2, TGFB3, JUP, RYR2, SCN1B, SCN3B, SCN4B, SCN5A, SLMAP, KCNJ2, DSP SNTA1, TGFB3, TMEM43 CDH2, CTNNA3, DES, DSC2, DSG2, DSP, JUP, Arrhythmogenic right ventricular cardio- SCN5A, LMNA, DSG2, TGFB3, JUP, LMNA, PKP2, PLN, RYR2, SCN5A, TGFB3, 5028 5, 6, 7, 8, 9, 10 myopathy panel RYR2, PKP2, DSC2, DSP TMEM43, TTN CACNA1C, CACNB2, GPD1L, HCN4, KCNE3, Brugada syndrome panel SCN5A 5062 5, 6, 7, 8, 9, 10 SCN1B, SCN3B, SCN5A, SLMAP ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CRYAB, CSRP3, DES, DMD, DNAJC19, DOLK, DSC2, DSG2, DSP, EMD, EYA4, FKTN, GATA4, MYBPC3, TNNT2, SGCD, MYH7, GATAD1, ILK, LAMA4, LAMP2, LDB3, LMNA, RAF1, BAG3, DMD, DSC2, DSG2, Cardiomyopathy dilated panel MURC, MYBPC3, MYH6, MYH7, MYPN, NEBL, 5005 5, 6, 7, 8, 9, 10 SCN5A, LMNA, PKP2, FKTN, DSP, NEXN, PDLIM3, PKP2, PLN, PRDM16, RAF1, GATA4 RBM20, SCN5A, SGCD, TAZ, TBX20, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, TXNRD2, VCL ACTC1, ACTN2, ANKRD1, CALR3, CAV3, CRYAB, CSRP3, DES, FHL2, FLNC, GLA, JPH2, LAMP2, LDB3, MYBPC3, MYH6, MYH7, MYL2, MYBPC3, MYH7, SLC25A4, Cardiomyopathy hypertrophic panel 5004 5, 6, 7, 8, 9, 10 MYL3, MYLK2, MYPN, NEXN, PDLIM3, PLN, TNNT2, CAV3, GLA PRKAG2, SLC25A4, SOS1, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TRIM63, TTN, TTR, VCL Catecholaminergic polymorphic ventricular RYR2, CASQ2, KCNJ2 RYR2, KCNJ2 5007 5, 6, 7, 8, 9, 10 tachycardia panel Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes ABCA3, ACVRL1, AP3B1, ASCL1, BDNF, BLOC1S3, BLOC1S6, BMPR2, CCDC39, CCDC40, CFTR, CSF2RA, CSF2RB, DKC1, DNAAF1, DNAAF2, DNAH11, DNAH5, DNAI1, DNAI2, DNAL1, DOCK8, DTNBP1, EDN3, ACVRL1, BMPR2, CFTR, DKC1, EFEMP2, ELMOD2, ELN, ENG, FBLN5, FBN1, DNAH5, DNAI1, DOCK8, ELN, Comprehensive pulmonary disease panel 5331 5, 6, 9, 10 FLCN, FOXF1, GDNF, HPS1, HPS3, HPS4, ENG, FOXF1, STAT3, TERC, TERT, HPS5, HPS6, LTBP4, NKX2-1, NME8, NOP10, TSC1, TSC2 PARN, PHOX2B, RET, RSPH1, RSPH4A, RSPH9, RTEL1, SCNN1A, SCNN1B, SCNN1G, SERPI- NA1, SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD, SMAD9, STAT3, TERC, TERT, TINF2, TSC1, TSC2 CFC1, CITED2, CRELD1, FOXH1, GATA4, Congenital heart defects panel GATA6, GDF1, NKX2-5, NOTCH1, TBX1, NKX2-5, TBX1, CFC1, GATA4 5298 5, 6, 7, 8, 9, 10 TBX20, ZFPM2 AKAP9, ANK2, CACNA1C, CALM1, CALM2, KCNE2, SCN5A, CAV3, KCNQ1, Long QT syndrome panel CALM3, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, 5014 5, 6, 7, 8, 9, 10 KCNH2, KCNE1, KCNJ2 KCNJ5, KCNQ1, SCN4B, SCN5A, SNTA1, TRDN ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, Pulmonary hypertension panel FOXF1, ENG, BMPR2, ACVRL1 5338 5, 6, 7, 8, 10 ENG, FOXF1, GDF2, KCNA5, KCNK3, SMAD9

Test x Disease Gene OMIM Gene Available test methods code Alveolar capillary dysplasia with misalignment of pulmonary veins FOXF1 2048 601089 2, 4, 10, 11 Arrhythmogenic right ventricular cardiomyopathy type 1 TGFB3 1301 190230 2, 4, 10, 11 Arrhythmogenic right ventricular cardiomyopathy type 5 TMEM43 1302 612048 2, 4, 7, 8 Arrhythmogenic right ventricular cardiomyopathy type 8 DSP 1297 125647 2, 4, 7, 8, 10, 11 Arrhythmogenic right ventricular cardiomyopathy type 9 PKP2 1303 602861 2, 4, 7, 8, 10, 11 Arrhythmogenic right ventricular cardiomyopathy type 10 DSG2 1304 125671 2, 4, 7, 8, 10, 11 Arrhythmogenic right ventricular cardiomyopathy type 11 DSC2 1305 125645 2, 4, 7, 8, 10, 11 Arrhythmogenic right ventricular cardiomyopathy type 12 JUP 1306 173325 2, 4 Arrhythmogenic right ventricular dysplasia type 2 RYR2 1100 180902 2, 7, 8 Atrial fibrillation type 3 KCNQ1 148 607542 2, 4, 7, 8, 10, 11 Atrial fibrillation type 4 KCNE2 144 603796 2, 4, 10, 11 Atrial fibrillation type 6 NPPA 1308 108780 2, 4 Atrial fibrillation type 7 KCNA5 1307 176267 2, 4 Atrial fibrillation type 10 SCN5A 257 600163 2, 4, 7, 8, 10, 11 Atrial fibrillation type 11 GJA5 59 121013 2, 4 Atrial fibrillation type 12 ABCC9 1082 601439 2, 3, 4, 7, 8, 10, 11 Atrial septal defect type 3 MYH6 39 160710 2, 4, 7, 8 Atrial septal defect type 4 TBX20 2891 606061 2, 3, 4, 10, 11 Atrial septal defect type 5 ACTC1 7 102540 2, 4 Atrial septal defect type 8 CITED2 2890 602937 2, 4 Atrial septal defect type 9 GATA6 1040 601656 2, 3, 4, 10, 11 Atrioventricular septal defect type 4 GATA4 1209 600576 2, 4, 10, 11 Atrioventricular septal defect type 5 GATA6 1040 601656 2, 3, 4, 10, 11 Barth syndrome TAZ 1309 300394 2, 3, 4, 10, 11 Bicuspid aortic valve TIMP1 2224 305370 2, 4 Brugada syndrome type 1 SCN5A 257 600163 2, 4, 7, 8, 10, 11 Brugada syndrome type 2 GPD1L 1073 611778 2, 4 Brugada syndrome type 3 CACNA1C 1074 114205 2, 3, 4, 7, 8, 10, 11 Brugada syndrome type 4 CACNB2 1075 600003 2, 4, 7, 8 Brugada syndrome type 5 SCN1B 254 600235 2, 3, 4, 10, 11 Brugada syndrome type 6 KCNE3 1076 604433 2, 4 Brugada syndrome type 7 SCN3B 1310 608214 2, 4 Brugada syndrome type 8 HCN4 116 605206 2, 4 Brugada syndrome type 9 SLMAP 1545 602701 2, 4, 7, 8 Cardiac defects, CNOT3 related CNOT3 2287 604910 2, 4, 7, 8 Cardiac defects, PPP1R8 related PPP1R8 2352 602636 2, 4 Cardiac valvular dysplesia, X-linked FLNA 803 300017 2, 3, 4, 10, 11 Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency SCO2 1425 604272 2, 4, 10, 11 Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency type 2 COX15 1368 603646 2, 3, 4, 10, 11 Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency type 3 COA5 2833 613920 2, 4 Cardiofaciocutaneous syndrome BRAF 1078 164757 2, 4, 7, 8 Cardiofaciocutaneous syndrome KRAS 152 190070 2, 3, 4, 10, 11 Cardiofaciocutaneous syndrome type 3 MAP2K1 161 176872 2, 4 Cardiofaciocutaneous syndrome type 4 MAP2K2 162 601263 2, 3, 4, 10, 11 Cardiomyopathy, apical hypertrophic, and neuropathy, MT-ATP8 related MT-ATP8 2554 516070 4 Cardiomyopathy, dilated MYBPC3 174 600958 2, 4, 7, 8, 10, 11 Cardiomyopathy, dilated type 1 CRYAB 690 123590 2, 4 Cardiomyopathy, dilated type 1A LMNA 158 150330 2, 4, 7, 8, 10, 11 Cardiomyopathy, dilated type 1AA ACTN2 1683 102573 2, 4, 7, 8 Cardiomyopathy, dilated type 1BB DSG2 1304 125671 2, 4, 7, 8, 10, 11 Cardiomyopathy, dilated type 1C LDB3 157 605906 2, 4, 7, 8 Cardiomyopathy, dilated type 1CC NEXN 1684 613121 2, 4, 7, 8 Cardiomyopathy, dilated type 1D TNNT2 303 191045 2, 4, 7, 8, 10, 11 Cardiomyopathy, dilated type 1DD RBM20 1685 613171 2, 4, 7, 8 Cardiomyopathy, dilated type 1E SCN5A 257 600163 2, 4, 7, 8, 10, 11 Cardiomyopathy, dilated type 1EE MYH6 39 160710 2, 4, 7, 8 Cardiomyopathy, dilated type 1G TTN 309 188840 2, 3, 7, 8, 10 Cardiomyopathy, dilated type 1GG SDHA 1188 600857 2, 4, 7, 8, 10, 11 Cardiomyopathy, dilated type 1HH BAG3 30 603883 2, 4, 10, 11 Cardiomyopathy, dilated type 1I DES 741 125660 2, 3, 4, 10, 11 Cardiomyopathy, dilated type 1J EYA4 973 603550 2, 3, 4, 7, 8, 10, 11 Cardiomyopathy, dilated type 1KK MYPN 2803 608517 2, 4, 7, 8

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes COL4A1, COL4A2, GAA, MMP3, PKD1, PKD2, Dolichoectasia panel PKD1, PKD2, GAA 5253 5, 6, 7, 8, 9, 10 SLC2A10 ACTA2, BGN, CBS, LOX, MAT2A, MFAP5, Familial thoracic aortic aneurysm panel 5061 5, 6, 7, 8, 9 MYH11, MYLK Hereditary hemorrhagic telangiectasia ACVRL1, ENG, GDF2, SMAD4 ENG, SMAD4, ACVRL1 5282 5, 6, 7, 8, 9, 10 panel ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, Pulmonary hypertension panel FOXF1, ENG, BMPR2, ACVRL1 5338 5, 6, 7, 8, 10 ENG, FOXF1, GDF2, KCNA5, KCNK3, SMAD9

› Vascular Diseases

Test x Disease Gene OMIM Gene Available test methods code Angioedema, hereditary SERPING1 1105 606860 2, 4, 10, 11 Antithrombin III deficiency SERPINC1 1860 107300 2, 4, 10, 11 Aortic aneurysm, familial thoracic type 3 TGFBR2 295 190182 2, 4, 7, 8, 10, 11 Aortic aneurysm, familial thoracic type 4 MYH11 1102 160745 2, 3, 4, 7, 8, 10, 11 Aortic aneurysm, familial thoracic type 5 TGFBR1 294 190181 2, 4, 10, 11 Aortic aneurysm, familial thoracic type 6 ACTA2 6 102620 2, 3, 4, 10, 11 Aortic aneurysm, familial thoracic type 7 MYLK 1104 600922 2, 4, 7, 8 Aortic aneurysm, familial thoracic type 8 PRKG1 2688 176894 2, 4, 7, 8 Aortic aneurysm, familial thoracic, MAT2A related MAT2A 2487 601468 2, 4 Aortic valve disease type 1 NOTCH1 1449 190198 2, 3, 4, 7, 8, 10, 11 Aortic valve disease type 2 SMAD6 1450 602931 2, 3, 4, 10, 11 Arterial calcification type 1, generalized, infantile ENPP1 2236 173335 2, 3, 4, 7, 8, 10, 11 Arterial calcification type 2, generalized, infantile ABCC6 2334 603234 2, 4, 7, 8, 10, 11 Arterial Tortuosity Syndrome SLC2A10 272 606145 2, 3, 4, 10, 11 Atherosclerosis, SOAT1 related SOAT1 2323 102642 2, 4 Bernard Soulier syndrome type A1 GP1BA 67 606672 2, 4 Bernard Soulier syndrome type A2 GP1BA 67 606672 2, 4 Bernard Soulier syndrome type B GP1BB 68 138720 2, 4 Bernard Soulier syndrome type C GP9 69 173515 2, 4 CADASIL NOTCH3 188 600276 1, 2, 4, 7, 8, 10, 11 Capillary malformation-arteriovenous malformation RASA1 2232 139150 2, 4, 7, 8, 10, 11 CARASIL HTRA1 138 602194 2, 3, 4, 10, 11 Carotid intimal medial thickness type 1 PPARG 2566 601487 2, 4, 10, 11 Cerebral cavernous malformations type 1 KRIT1 52 604214 1, 2, 4, 7, 8, 10, 11 Cerebral cavernous malformations type 2 CCM2 53 607929 2, 4, 10, 11 Cerebral cavernous malformations type 3 PDCD10 54 609118 2, 4, 10, 11 Coarctation of the aorta MCTP2 2246 2, 4, 7, 8 Coronary artery disease in familial hypercholesterolemia, protection against ABCA1 2098 600046 2, 4, 7, 8 Fabry disease GLA 373 300644 2, 4, 10, 11, 14, 15 Factor II deficiency F2 374 176930 1, 2, 4, 7, 8 Factor VII deficiency F7 2385 613878 2, 4, 10, 11 Glycoprotein Ia C807T polymorphism ITGA2 1110 192974 2, 4, 7, 8 Hemorrhagic destruction of the brain, subependymal calcification, and cataracts JAM3 2771 606871 2, 4 Homocystinuria MTHFR 1112 607093 2, 4, 10, 11 Homocystinuria due to cystathionine beta-synthase deficiency CBS 1111 613381 2, 3, 4, 7, 8, 10, 11 Homocystinuria-megaloblastic anemia, cbl E type MTRR 982 602568 2, 4, 7, 8 Hypertension early onset NR3C2 82 600983 2, 3, 4, 7, 8, 10, 11 Hypertension, ADD2 related ADD2 2107 102681 2, 4 Hypertension, salt-sensitive essential, susceptibility to CYP3A5 2518 605325 2, 4, 7, 8, 10, 11 Loeys-Dietz syndrome type 4 TGFB2 889 190220 2, 3, 4, 10, 11 Moyamoya disease type 2, susceptibility to RNF213 119 613768 2, 3, 7, 8, 10 Moyamoya type 6 with achalasia GUCY1A3 2809 139396 2, 4 Myoglobinuria acute recurrent LPIN1 562 605518 2, 3, 4, 7, 8, 10, 11 Myopathy with lactic acidosis hereditary ISCU 667 611911 1, 2, 4

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code ADAMTS13, C3, CD46, CFB, CFH, CFHR1, CFH, CFHR1, CFHR2, CFHR3, Atypical hemolytic uremic syndrome panel CFHR2, CFHR3, CFHR5, CFI, DGKE, MMACHC, 5202 7, 8 CFHR5 PIGA, PLG, THBD ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CCDC28B, CEP290, Bardet Biedl panel 5003 5, 6, 7, 8, 9 IFT27, LZTFL1, MKKS, MKS1, SDCCAG8, TMEM67, TRIM32, TTC8, WDPCP ATP6V1B1, BSND, CA2, CASR, CLCNKA, CLCNKB, CLDN16, CLDN19, FXYD2, HS- SLC12A3, CLCNKA, CLCNKB, Bartter Syndrome panel D11B2, KCNJ1, KCNJ10, KLHL3, NR3C2, SCN- 5089 5, 6, 7, 8, 9, 10 CASR N1A, SCNN1B, SCNN1G, SLC12A1, SLC12A2, SLC12A3, SLC4A1, SLC4A4, WNK1, WNK4 Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes Combined pituitary hormone deficiency GHR, HESX1, LHX3, LHX4, OTX2, POU1F1, GHR, HESX1, POU1F1, PROP1, 5303 5, 6, 7, 8, 9, 10 panel PROP1 LHX3, LHX4 CYP21A2, CYP17A1, CYP11B1, HSD3B2, POR, Congenital adrenal hyperplasia panel CYP17A1, POR 5271 7, 8, 10 STAR ACTN4, CD2AP, INF2, NPHS1, NPHS2, TRPC6, Focal Glomerulonephrosis panel WT1 5205 5, 6, 7, 8, 9, 10 WT1 Intrahepatic cholestasis panel ABCB11, ABCB4, ATP8B1, UGT1A1 ABCB4 5267 5, 6, 7, 8, 9, 10 ANOS1, CHD7, DUSP6, FEZF1, FGF17, FGF8, FGFR1, FLRT3, FSHB, GNRH1, GNRHR, HESX1, CHD7, FGFR1, GNRH1, GNRHR, Kallmann syndrome and Hypogonadotro- HS6ST1, IL17RD, KISS1, KISS1R, LHB, NSMF, HESX1, ANOS1, KISS1R, PROK2, 5339 5, 6, 7, 8, 9, 10 pic hypogonadism panel PROK2, PROKR2, SEMA3A, SPRY4, TAC3, PROKR2 TACR3, WDR11 Maple syrup urine disease panel BCKDHA, BCKDHB, DBT, DLD 5068 5, 6, 7, 8, 9 MKS1, TMEM216, TMEM67, CEP290, RPGRI- Meckel syndrome panel P1L, CC2D2A, NPHP3, TCTN2, B9D1, B9D2, 5220 5, 6, 7, 8, 9 TMEM231 Neonatal mitochondrial hepatopathies BCS1L, DGUOK, FAH, GFM1, HAMP, MPV17, TFR2, DGUOK, MPV17, RRM2B, 5306 5, 6, 7, 8, 9, 10 panel NBAS, POLG, RRM2B, TFR2, TRMU POLG, HAMP NPHP1, INVS, NPHP3, NPHP4, ANKS6, IQCB1, Nephronophthisis panel CEP164, CEP290, GLIS2, RPGRIP1L, NEK8, NPHP1 5041 5, 6, 7, 8, 9, 10 SDCCAG8, ZNF423 ARHGDIA, DGKE, LAMB2, NPHS1, NPHS2, Nephrotic syndrome panel WT1 5096 5, 6, 7, 8, 9, 10 PLCE1, WT1 Pancreatitis panel CFTR, CPA1, CTRC, PRSS1, SPINK1 SPINK1, CFTR, PRSS1 5002 5, 6, 7, 8, 9, 10 Polycystic kidney panel BICC1, PKD1, PKD2, NOTCH2, PKHD1 PKD1, PKD2, PKHD1 5053 7, 10 CUL3, HSD11B2, KLHL3, NR3C2, SCNN1A, Pseudohypoaldosteronism panel 5269 5, 6, 7, 8, 9 SCNN1B, SCNN1G, WNK1, WNK4 ATP6V0A4, ATP6V1B1, CA2, EHHADH, HN- Renal tubular acidosis panel HNF4A 5320 5, 6, 7, 8, 9, 10 F4A, SLC34A1, SLC4A1, SLC4A4

Test x Disease Gene OMIM Gene Available test methods code 17-beta hydroxysteroid dehydrogenase X deficiency HSD17B10 134 300256 2, 4 Achalasia addisonianism alacrimia syndrome AAAS 121 605378 2, 3, 4, 7, 8, 10, 11 Acromegaly, predisposition to, due to germline GPR101 mutation GPR101 2740 300393 2, 4 Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete CYP11A1 2095 118485 2, 4 Adrenocorticotropic hormone deficiency TBX19 2513 604614 2, 4 Alport syndrome, autosomal recessive COL4A3 983 120070 2, 4, 7, 8, 10, 11 Alport syndrome, autosomal recessive COL4A4 984 120131 2, 4, 7, 8, 10, 11 Alport syndrome, X-Linked COL4A5 985 303630 2, 4, 7, 8, 10, 11 Androgen insensitivity AR 20 313700 2, 4, 7, 8, 10, 11, 12 Androgen insensitivity, partial, with or without breast cancer AR 20 313700 2, 4, 7, 8, 10, 11, 12 Androgen-binding protein deficiency SHBG 2787 182205 2, 4 Arthrogryposis, renal dysfunction, and cholestasis type 2 VIPAS39 2467 613401 2, 3, 4, 7, 8, 10, 11 Bardet-Biedl syndrome type 1 BBS1 31 209901 2, 4, 7, 8 Bardet-Biedl syndrome type 2 BBS2 35 606151 2, 3, 4, 7, 8, 10, 11 Bardet-Biedl syndrome type 3 ARL6 22 608845 2, 4 Bardet-Biedl syndrome type 4 BBS4 36 600374 2, 4, 7, 8 Bardet-Biedl syndrome type 5 BBS5 1120 603650 2, 3, 4, 7, 8, 10, 11 Bardet-Biedl syndrome type 6 MKKS 166 604896 2, 3, 4, 10, 11 Bardet-Biedl syndrome type 7 BBS7 1121 607590 2, 4, 7, 8 Bardet-Biedl syndrome type 8 TTC8 308 608132 2, 4, 7, 8 Bardet-Biedl syndrome type 9 BBS9 1122 607968 2, 4, 7, 8 Bardet-Biedl syndrome type 10 BBS10 32 610148 2, 4 Bardet-Biedl syndrome type 11 TRIM32 307 602290 2, 4 Bardet-Biedl syndrome type 12 BBS12 33 610683 2, 4 Bardet-Biedl syndrome type 13 MKS1 34 609883 2, 3, 4, 7, 8, 10, 11 Bardet-Biedl syndrome type 14 CEP290 642 610142 2, 3, 4, 10, 11 Bardet-Biedl syndrome type 15 WDPCP 1326 613580 2, 4, 7, 8 Bardet-Biedl syndrome, LZTFL1 related LZTFL1 500 606568 2, 4 Bardet-Biedl syndrome, modifier of, CCDC28B related CCDC28B 58 610162 2, 4 Bartter syndrome SLC12A2 1695 600840 2, 4, 7, 8 Bartter syndrome SLC12A3 1130 600968 2, 4, 7, 8, 10, 11 Bartter syndrome SLC12A5 1697 606726 2, 4, 7, 8 Bartter syndrome SLC12A7 1698 604879 2, 4 Bartter syndrome type 1 SLC12A1 1691 600839 2, 3, 4, 7, 8, 10, 11 Bartter syndrome type 2 KCNJ1 1692 600359 2, 4, 10, 11 Bartter syndrome type 3 CLCNKB 1514 602023 2, 4, 7, 8, 10, 11 Bartter syndrome type 4a BSND 1693 606412 2, 4 Bartter syndrome type 4b CLCNKA 1694 602024 2, 4 Cholestasis, infantile, NR1H4 related NR1H4 2853 603826 2, 4 Crigler-Najjar syndrome, type 1 UGT1A1 1448 191740 2, 3, 4, 10, 11 Crigler-Najjar syndrome, type 2 UGT1A1 1448 191740 2, 3, 4, 10, 11 Cryptorchidism RXFP2 2390 606655 2, 4, 7, 8 Cystinosis, nephropathic CTNS 371 606272 2, 3, 4, 10, 11 Cystinuria PREPL 1743 609557 2, 4, 7, 8, 10, 11 Cystinuria SLC3A1 1124 104614 2, 4, 7, 8, 10, 11 Cystinuria SLC7A9 1125 604144 2, 4, 7, 8, 10, 11 Dent disease CLCN5 1840 300008 2, 3, 4, 7, 8, 10, 11 Diabetes insipidus, nephrogenic, autosomal AQP2 19 107777 2, 3, 4, 10, 11 Dubin-Johnson syndrome ABCC2 1126 601107 2, 3, 4, 7, 8, 10, 11 Epstein syndrome MYH9 179 160775 2, 4, 7, 8, 10, 11 Estrogen resistance ESR1 2532 133430 2, 4, 7, 8 Factor XI deficiency F11 1815 264900 2, 4, 7, 8, 10, 11 Factor XII deficiency F12 1816 610619 2, 3, 4, 7, 8, 10, 11 Factor XIIIA deficiency F13A1 2272 134570 2, 3, 4, 7, 8, 10, 11 Fanconi renotubular syndrome type 2 SLC34A1 1776 182309 2, 4 Fanconi-Bickel syndrome SLC2A2 390 138160 2, 3, 4, 10, 11 Focal segmental glomerulosclerosis and dilated cardiomyopath, MT-TY related MT-TY 2561 590100 4 Focal segmental glomerulosclerosis type 1 ACTN4 8 604638 2, 4, 7, 8 Focal segmental glomerulosclerosis type 2 TRPC6 1128 603652 2, 4, 7, 8 Focal segmental glomerulosclerosis type 3 CD2AP 1512 604241 2, 4, 7, 8 Focal segmental glomerulosclerosis type 4, susceptibility to APOL1 2725 603743 2, 4 Focal segmental glomerulosclerosis type 5 INF2 1129 610982 2, 3, 4, 7, 8, 10, 11

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code CentoArray Cyto™ 750K Genome-wide aCGH with 750,000 markers 50068 7 CentoArray Cyto™ HD Genome-wide aCGH with 2.5 million markers 50001 7 Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes CentoScreen™ DUO Analysis of 331 genes for carrier screening 50098 5 Complete panel evaluation of 331 genes for CentoScreen™ Paired PACK first partner + risk gene analysis for second 50097 5 partner based on the result of first partner Risk gene analysis for second partner based CentoScreen™ Paired X-TRA on the findings of first partner when ordered 50099 5 separately CentoScreen™ SOLO Analysis of 331 genes for carrier screening 50096 5 BMP15, CYP21A2, FSHR, LHB, LHCGR, TUBB8, Female infertility panel CYP21A2 5243 7 ZP1 AR, CATSPER1, CFTR, FSHB, FSHR, HESX1, AR, CFTR, HESX1, NR5A1, Global infertility panel 5201 7, 10 LHB, LHCGR, NR5A1, POU1F1, SRY POU1F1 Male infertility panel AR, CATSPER1, CFTR, FSHR, LHCGR CFTR, AR 5242 7, 10

› Reproductive Genetics

Test x Disease Gene OMIM Gene Available test methods code 46,XX sex reversal type 1 SRY 1880 480000 2, 4, 10, 11 46,XY sex reversal type 8, modifier of AKR1C4 2659 600451 2, 4 Aromatase deficiency CYP19A1 1511 107910 2, 3, 4, 10, 11 Azoospermia induced by Y chromosome microdeletions AZF region 1881 10 Congenital bilateral absence of vas deferens CFTR 370 602421 2, 7, 10, 11 Cryptorchidism RXFP2 2390 606655 2, 4, 7, 8 Deafness and male infertility STRC 958 606440 2, 3, 4, 10, 11 Deafness and male infertility, CATSPER2 related CATSPER2 1233 607249 2, 4 Disorders of sex development with cleft palate FOXF2 2049 603250 2, 4, 10, 11 Follicle-stimulating hormone deficiency, isolated FSHB 1772 136530 2, 4, 10, 11 Guttmacher syndrome HOXA13 2913 142959 2, 4 Hand-foot-uterus syndrome HOXA13 2913 142959 2, 4 Hydatidiform mole NLRP7 1744 609661 2, 3, 4, 10, 11 Hydatidiform mole, recurrent, type 2 KHDC3L 1745 611687 2, 3, 4, 10, 11 Hypogonadotropic hypogonadism KISS1 1154 603286 2, 4, 10, 11 Hypogonadotropic hypogonadism NSMF 1132 608137 2, 3, 4, 7, 8, 10, 11 Hypogonadotropic hypogonadism type 6 with or without anosmia FGF8 1235 600483 2, 3, 4, 10, 11 Hypogonadtropic hypogonadism type 14 WDR11 1447 606417 2, 3, 4, 7, 8, 10, 11 Hypospadias type 1, X-linked AR 20 313700 2, 4, 7, 8, 10, 11, 12 Hypospadias type 2, X-linked MAMLD1 1199 300120 2, 3, 4, 7, 8, 10, 11 Leydig cell hypoplasia type 1 LHCGR 80 152790 2, 3, 4, 7, 8, 10, 11 Oligo-astheno-teratozoospermia NANOS1 1535 608226 2, 4 Oocyte maturation defect ZP1 2389 195000 2, 4, 7, 8 Oogenesis dysfunction SOHLH1 474 610224 2, 4 Ovarian dysgenesis type 1 FSHR 1773 136435 2, 3, 4, 10, 11 Ovarian dysgenesis type 2 BMP15 2388 300247 2, 4 Persistent Mullerian duct syndrome type 1 AMH 1833 600957 2, 3, 4, 10, 11 Persistent Mullerian duct syndrome type 2 AMHR2 1834 600956 2, 3, 4, 7, 8, 10, 11 Preeclampsia/eclampsia type 5 CORIN 2613 605236 2, 4, 7, 8 Pregnancy loss, recurrent, C4BPA related C4BPA 2614 120830 2, 4, 7, 8 Pseudohermaphroditism with gynecomastia HSD17B3 2088 605573 2, 4 SPGF4 SYCP3 1157 604759 2, 4 SPGF5 AURKC 1158 603495 2, 4 SPGF6 SPATA16 1159 609856 2, 3, 4, 10, 11 SPGF7 CATSPER1 1160 606389 2, 4 SPGF8 NR5A1 1161 184757 2, 4, 10, 11 SPGF9 DPY19L2 1162 613893 2, 4, 7, 8 Testicular anomalies with or without congenital heart disease GATA4 1209 600576 2, 4, 10, 11

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code Afibrinogenemia panel FGA, FGB, FGG 5279 5, 6, 7, 8, 9 BLNK, BTK, CD79A, CD79B, IGHM, IGLL1, Agammaglobulinemia panel BTK, SH2D1A 5256 5, 6, 7, 8, 9, 10 LRRC8A, PIK3R1, SH2D1A ADA, AK2, DCLRE1C, LIG4, NHEJ1, RAC2, B-negative SCID panel DCLRE1C, RAG2 5257 5, 6, 7, 8, 9, 10 RAG1, RAG2 ABCB7, AK2, ALAS2, ANKRD26, BRCA2, BRIP1, CASP10, CBL, CDAN1, CSF3R, CXCR4, DKC1, ELANE, ERCC4, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, G6PC3, GATA1, GFI1, HAX1, PALB2, FANCD2, CXCR4, FANCB, HOXA11, JAGN1, KLF1, LYST, MASTL, MPL, RPL35A, RPS17, RPL11, DKC1, MYH9, NBN, NHP2, NOP10, PALB2, PARN, Bone marrow failure panel TERC, TERT, RPL5, STX11, BRIP1, 5325 5, 6, 7, 8, 9, 10 PRF1, PUS1, RAC2, RAD51C, RPL11, RPL15, RPS19, MYH9, RPS26, PRF1, RPL26, RPL27, RPL35A, RPL5, RPS10, RPS17, BRCA2, RAD51C, FANCA RPS19, RPS24, RPS26, RPS27, RPS28, RPS29, RPS7, RTEL1, SBDS, SEC23B, SLC19A2, SLC25A38, SLC46A1, SLX4, SRP72, STX11, STXBP2, TCN2, TERC, TERT, TINF2, UBE2T, VPS45, WAS, WRAP53, XRCC2 CD3D, CD3E, CD247, FOXN1, IL2RG, IL7R, B-positive SCID panel JAK3, ORAI1, PNP, PTPRC, RMRP, STAT5B, STAT5B, TBX1 5258 5, 6, 7, 8, 9, 10 STIM1, TBX1, ZAP70 Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio 50089 5, 6 ciated with known clinical phenotypes Targets exonic regions of ~6700 genes asso- CentoDx™ Trio Plus 50090 5 ciated with known clinical phenotypes ADA, AK2, CD3D, CD3E, CD247, DCLRE1C, FOXN1, IL2RG, IL7R, JAK3, LIG4, NHEJ1, Comprehensive SCID panel TBX1, RAG2, DCLRE1C, STAT5B 5259 5, 6, 7, 8, 9, 10 ORAI1, PNP, PTPRC, RAC2, RAG1, RAG2, RMRP, STAT5B, STIM1, TBX1, ZAP70 Congenital dyserythropoietic anemia panel C15orf41, CDAN1, GATA1, KLF1, SEC23B 5328 5, 6, 7, 8, 9 CSF3R, CXCR4, ELANE, G6PC3, GFI1, HAX1, Congenital neutropenia panel 5318 5, 6, 7, 8, 9 JAGN1, RAC2, SBDS, VPS45, WAS ABCB7, ALAS2, GLRX5, PUS1, SLC19A2, Congenital sideroblastic anemia panel 5300 5, 6, 7, 8, 9 SLC25A38, TRNT1, YARS2 CLDN16, CLDN19, CNNM2, EGF, FXYD2, Hypomagnesemia panel SLC12A3, KCNA1 5274 5, 6, 7, 8, 9, 10 KCNA1, SLC12A3, TRPM6 Megaloblastic anemia panel AMN, CUBN, GIF 5074 5, 6, 7, 8, 9 MAX, PRKAR1A, SDHA, SDHAF2, SDHB, SDHA, VHL, SDHD, SDHAF2, MAX, Pheochromocytoma panel 5019 5, 6, 7, 8, 9, 10 SDHC, SDHD, TMEM127, VHL SDHB, SDHC Spherocytosis panel ANK1, EPB42, SLC4A1, SPTA1, SPTB 5117 5, 6, 7, 8, 9 ADAMTS13, ANKRD26, CYCS, GATA1, GP1BA, Thrombocytopenia panel GP1BB, GP9, ITGA2B, ITGB3, MASTL, MPL, MYH9, RUNX1 5073 5, 6, 7, 8, 9, 10 MYH9, RUNX1, WAS

Test x Disease Gene OMIM Gene Available test methods code Accelerated tumor formation, susceptibility to MDM2 2144 164785 2, 4, 7, 8, 10, 11 Adenosine triphosphate, elevated, of erythrocytes PKLR 481 609712 2, 4, 10, 11 Afibrinogenemia, congenital FGA 2091 134820 2, 4 Afibrinogenemia, congenital FGB 2092 134830 2, 3, 4, 10, 11 Afibrinogenemia, congenital FGG 2093 134850 2, 4, 7, 8 Agammaglobulinemia and isolated hormone deficiency BTK 2024 300300 2, 4, 7, 8, 10, 11 Agammaglobulinemia type 1, autosomal recessive IGHM 2552 147020 2, 4 Agammaglobulinemia type 1, X-linked BTK 2024 300300 2, 4, 7, 8, 10, 11 Agammaglobulinemia type 2, autosomal recessive IGLL1 2553 146770 2, 4 Agammaglobulinemia type 3, autosomal recessive CD79A 2550 112205 2, 4 Agammaglobulinemia type 4, autosomal recessive BLNK 2606 604515 2, 4, 7, 8 Agammaglobulinemia type 5, autosomal recessive LRRC8A 2525 608360 2, 4 Agammaglobulinemia type 6, autosomal recessive CD79B 2551 147245 2, 4 Agammaglobulinemia type 7, autosomal recessive PIK3R1 2523 171833 2, 4, 7, 8 Alpha-thalassemia/mental retardation syndrome ATRX 27 300032 2, 4, 7, 8, 10, 11 Anemia, neonatal hemolytic, fatal and near-fatal SPTB 1855 182870 2, 4, 7, 8 Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive GLRX5 2315 609588 2, 4 Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive SLC25A38 2904 610819 2, 4 Anemia, sideroblastic, with ataxia ABCB7 2729 300135 2, 4, 7, 8 Anemia, sideroblastic, X-linked ALAS2 2783 301300 2, 4 Anemia, X-linked GATA1 66 305371 2, 3, 4, 10, 11 Anhaptoglobinemia HP 2789 140100 2, 4 Bleeding disorder, platelet-type 8 P2RY12 2860 600515 2, 4 Bleeding disorder, platelet-type 15 ACTN1 2603 102575 2, 4, 7, 8 Bleeding disorder, platelet-type 17 GFI1B 2837 604383 2, 4 Bone marrow failure syndrome type 1 SRP72 756 602122 2, 3, 4, 7, 8, 10, 11 Bone marrow failure syndrome type 2 ERCC6L2 2858 615667 2, 4, 7, 8 Cyanosis, transient neonatal HBG2 2757 142250 2, 4, 10, 11 Dehydrated hereditary stomatocytosis PIEZO1 635 611184 2, 3, 4, 10, 11 Delta-beta thalassemia HBB 112 141900 2, 4, 10, 11 Diamond Blackfan anemia type 15 with mandibulofacial dysostosis RPS28 2699 603685 2, 3, 4, 10, 11 Diamond-Blackfan anemia type 1 RPS19 1498 603474 2, 4, 10, 11 Diamond-blackfan anemia type 3 RPS24 1565 602412 2, 4 Diamond-Blackfan anemia type 4 RPS17 1564 180472 2, 4, 10, 11 Diamond-Blackfan anemia type 5 RPL35A 1561 180468 2, 4, 10, 11 Diamond-Blackfan anemia type 6 RPL5 1243 603634 2, 4, 10, 11 Diamond-Blackfan anemia type 7 RPL11 1560 604175 2, 4, 10, 11 Diamond-Blackfan anemia type 8 RPS7 1563 603658 2, 4 Diamond-Blackfan anemia type 9 RPS10 1562 603632 2, 4 Diamond-Blackfan anemia type 10 RPS26 1566 603701 2, 4, 10, 11 Diamond-Blackfan anemia type 11 RPL26 2696 603704 2, 3, 4, 10, 11 Diamond-Blackfan anemia type 12 RPL15 2793 604174 2, 3, 4, 10, 11 Diamond-Blackfan anemia type 13 RPS29 2697 603633 2, 3, 4, 10, 11 Diamond-Blackfan anemia type 14 with mandibulofacial dysostosis TSR2 2698 300945 2, 3, 4, 10, 11 Dyserythropoietic anemia COX4I2 1030 607976 2, 4 Dyserythropoietic anemia, congenital, type 1B C15orf41 2036 615626 2, 3, 4, 7, 8, 10, 11 Dyserythropoietic anemia, congenital, type 3 KIF23 2182 605064 2, 3, 4, 7, 8, 10, 11 Dyserythropoietic anemia, congenital, type 4 KLF1 2177 600599 2, 3, 4, 10, 11 Dysprothrombinemia F2 374 176930 1, 2, 4, 7, 8 Erythrocytosis, familial type 1 EPOR 2800 133171 2, 3, 4, 10, 11 Erythrocytosis, familial type 3 EGLN1 1798 606425 2, 3, 4, 10, 11 Erythrocytosis, familial type 4 EPAS1 1706 603349 2, 3, 4, 7, 8, 10, 11 Factor X deficiency F10 2170 613872 2, 4, 10, 11 Favism, susceptibility to G6PD 400 305900 2, 3, 4, 7, 8, 10, 11 Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative CYBA 2172 608508 2, 4 Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 NCF2 2173 608515 2, 4, 7, 8 Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 NCF4 2174 601488 2, 4 Granulomatous disease, chronic, X-linked CYBB 998 300481 2, 3, 4, 7, 8, 10, 11 Hemolytic anemia due to G6PD deficiency G6PD 400 305900 2, 3, 4, 7, 8, 10, 11 Hemolytic anemia due to triosephosphate isomerase deficiency TPI1 2902 190450 2, 4 Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy CD59 2663 107271 2, 4 Hemolytic anemia, Kell-system related KEL 2812 613883 2, 4, 7, 8

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code TPM2, MYBPC1, MYH3, TNNT3, TNNI2, MYH8, Arthrogryposis panel 5033 5, 6, 7, 8, 9 FBN2, PIEZO2, ECEL1, DOK7, RAPSN ABCC8 (c.3989-9G>A, p.F1387del (NM_000352.3)), ASPA (p.Y231X, p.E285A, p.A305E (NM_001128085.1)), BCKDHB (c.548G>C, c.832G>A, c.1114G>T (NM_183050.2)), BLM (c.2207_2212delATCTGAinsTAGATTC (NM_000057.2)), BRCA1 (c.68_69delAG, c.5266dupC (NM_007294.3)), BRCA2 (c.5946delT (NM_000059.3 2)), CFTR (c.1521_1523delCTT, c.1519_1521delATC, c.3454G>C, c.3846G>A, c.3718-2477C>T, c.3909C>G, c.2988+1G>A, c.350G>A, c.1000C>T, c.254G>A, c.1364C>A, c.2052del, c.1624G>T, c.1585-1G>A (NM_000492.3)), Ashkenazi panel (basic) 5116 5 DLD (c.104dupA, c.685G>T (NM_000108.3)), FANCC (c.456+4A>T, NM_000136.2), G6PC (c.247C>T (NM_000151.3)), GBA (c.84dupG, c.115+1G>A, c.1448T>C, c.1226A>G, c.1604G>A, c.1297G>T (NM_001005741.2)), HEXA (c.1274_1277dupTATC, c.1421+1G>C, c.805G>A, c.739C>T, c.745C>T (NM_000520.4)), IKBKAP (c.2204+6T>C (NM_003640.3)), MCOLN1 (c.406-2A>G, 6.4kb del/ g.511_6943del (exon 01 to part exon 07) (NM_020533.2)), SMPD1 (c.996delC, c.911T>C, c.1493G>T, c.1829_1831delGCC (NM_000543.4)), TMEM216 (c.218G>T, (NM_001173991.2)) ABCC8 (c.3989-9G>A, p.F1387del (NM_000352.3)), ASPA (c.433- 2A>G, p.Y231X, p.E285A, p.A305E (NM_001128085.1)), BCKDHB (c.548G>C, c.832G>A, c.1114G>T (NM_183050.2)), BLM (c.2207_2212delATCTGAinsTAGATTC (NM_000057.2)), BRCA1 (c.68_69delAG, c.5266dupC (NM_007294.3)), BRCA2 (c.5946delT (NM_000059.3 2)), CFTR (c.1521_1523delCTT, c.1519_1521delATC, c.3454G>C, c.3846G>A, c.3718-2477C>T, c.3909C>G, c.3808G>A, c.1040G>A, c.1865G>A, c.489+1G>T, c.1657C>T, c.262_263del, c.1652G>A, c.2988+1G>A, c.350G>A, c.579+1G>T, c.1000C>T, c.1679G>C, c.3484C>T, c.3528delC, c.254G>A, c.1364C>A, c.2052del, c.1766+1G>A, c.443T>C, 1078delT, c.1624G>T, c.2657+5G>A, c.1585-1G>A, c.178G>T (NM_000492.3)), CLRN1 (c.144T>G (NM_174878.2)), DLD (c.104dupA, c.685G>T (NM_000108.3)), FANCC (c.67delG, c.456+4A>T, NM_000136.2), G6PC (c.247C>T (NM_000151.3)), GBA (c.84dupG, Ashkenazi panel (advanced) 5110 5 c.115+1G>A, c.1448T>C, c.1226A>G, c.1604G>A, c.1297G>T (NM_001005741.2)), HEXA (c.1274_1277dupTATC, c.1421+1G>C, c.805G>A, c.739C>T, c.745C>T (NM_000520.4)), IKBKAP (c.2204+6T>C, c.2087G>C (NM_003640.3)), MCOLN1 (c.406-2A>G, 6.4kb del/ g.511_6943del (exon 01 to part exon 07) (NM_020533.2)), NEB (p.R2478_ D2512del/ c.7431+1917_7536+372del (exon 55 deletion))(NM_001271208.1)), PCDH15 (c.733C>T, (NM_033056.3)), SMPD1 (c.996delC, c.911T>C, c.1493G>, c.1829_1831delGCC (NM_000543.4)), PKHD1 (c.3761 (NM_138694.3)), TMEM216 (c.218G>T, (NM_001173991.2)), MPL (c.79+2T>A (NM_005373.2), CPT2 (c.338C>T, c.1239_1240del, c.1342T>C (NM_000098.2)), PMM2 (c.422G>A, c.338C>T, c.357C>A, c.691G>A (NM_000303.2)), FAH (c.782C>T (NM_000137.2)), FKTN (c.1167dup (NM_001079802.1)), ATP7B (c.3191A>C, c.3207C>A, c.2333G>T, c.1934T>G (NM_000053.2)) CentoArray Cyto™ 750K Genome-wide aCGH with 750,000 markers 50068 7 CentoArray Cyto™ HD Genome-wide aCGH with 2.5 million markers 50001 7 Targets exonic regions of ~6700 genes asso- CentoDx™ Solo 50088 5, 6 ciated with known clinical phenotypes

Test x Disease Gene OMIM Gene Available test methods code Achondrogenesis type 2 COL2A1 943 120140 2, 4, 7, 8, 10, 11 Acrodysostosis type 1, with or without hormone resistance PRKAR1A 1192 188830 2, 3, 4, 10, 11 Acromelic frontonasal dysostosis ZSWIM6 2454 615951 2, 3, 4, 10, 11 Acromesomelic dysplasia, Maroteaux type NPR2 1969 108961 2, 3, 4, 7, 8, 10, 11 Acromicric dysplasia FBN1 950 134797 2, 7, 8, 10 Adams-Oliver syndrome type 6 DLL4 3049 605185 2, 4 ADULT syndrome, split hand-foot malformation TP63 304 603273 2, 3, 4, 7, 8, 10, 11 Alacrima, achalasia and mental retardation syndrome GMPPA 2162 615495 2, 4 Alagille syndrome type 1 JAG1 1206 601920 2, 4, 7, 8, 10, 11 Alagille syndrome type 2 NOTCH2 1207 600275 2, 3, 4, 7, 8, 10, 11 Alazami syndrome LARP7 2187 612026 2, 3, 4, 7, 8, 10, 11 Alpha-thalassemia/mental retardation syndrome ATRX 27 300032 2, 4, 7, 8, 10, 11 Ankyloblepharon-ectodermal defects-cleft lip/palate TP63 304 603273 2, 3, 4, 7, 8, 10, 11 Anterior segment mesenchymal dysgenesis PITX3 2571 602669 2, 4 Antley-Bixler syndrome FGFR2 1730 176943 2, 4, 7, 8, 10, 11 Apert syndrome FGFR2 1730 176943 2, 4, 7, 8, 10, 11 Athabaskan brainstem dysgenesis syndrome HOXA1 1208 142955 2, 4, 10, 11 Atrial septal defect type 2 GATA4 1209 600576 2, 4, 10, 11 Atrial septal defect with atrioventricular conduction defects NKX2-5 1210 600584 2, 4, 10, 11 Atrioventricular septal defect, partial with heterotaxy syndrome CRELD1 2039 607170 2, 4 Auriculocondylar syndrome type 1 GNAI3 2916 139370 2, 3, 4, 10, 11 Auriculocondylar syndrome type 2 PLCB4 1015 600810 2, 3, 4, 7, 8, 10, 11 Axenfeld-Rieger syndrome type 1 PITX2 216 601542 2, 4, 10, 11 Axenfeld-Rieger syndrome type 3 FOXC1 888 601090 2, 4, 10, 11 Bainbridge-Ropers syndrome ASXL3 2111 615115 2, 4, 7, 8 Baller-Gerold syndrome RECQL4 239 603780 2, 3, 4, 7, 8, 10, 11 Band-like calcification with simplified gyration and polymicrogyria OCLN 1710 602876 2, 3, 4, 10, 11 Baraitser-Winter syndrome type 1 ACTB 779 102630 2, 3, 4, 10, 11 Baraitser-Winter syndrome type 2 ACTG1 989 102560 2, 3, 4, 10, 11 Basal cell nevus syndrome PTCH1 1216 601309 2, 4, 7, 8, 10, 11 Basal cell nevus syndrome SUFU 2360 607035 2, 3, 4, 7, 8, 10, 11 Basal ganglia calcification type 1, ideopathic SLC20A2 1329 158378 2, 3, 4, 10, 11 Basal ganglia calcification type 4 PDGFRB 1939 173410 2, 3, 4, 10, 11 Basal ganglia calcification type 5, idiopathic PDGFB 1801 190040 2, 3, 4, 10, 11 Basal ganglia calcification type 6, idiopathic XPR1 2881 605237 2, 3, 4, 10, 11 Beta-ureidopropionase deficiency UPB1 2466 606673 2, 3, 4, 10, 11 Bifid nose FREM1 1534 608944 2, 3, 4, 7, 8, 10, 11 Birt-Hogg-Dube syndrome FLCN 55 607273 1, 2, 4, 10, 11 Bjornstad syndrome BCS1L 1423 603647 2, 3, 4, 10, 11 Blau syndrome NOD2 2310 605956 2, 3, 4, 7, 8, 10, 11 Bohring-Opitz syndrome ASXL1 2280 612990 2, 3, 4, 7, 8, 10, 11 Bone marrow failure syndrome type 2 ERCC6L2 2858 615667 2, 4, 7, 8 Brachydactyly type A1C GDF5 1920 601146 2, 4, 10, 11 Brachydactyly type A2 BMP2 1491 112261 2, 4 Brachydactyly type A2 BMPR1B 1324 603248 2, 4 Brachydactyly type B1 ROR2 244 602337 2, 4, 7, 8, 10, 11 Brachydactyly type E1 HOXD13 1975 142989 2, 4, 10, 11 Brachydactyly-mental retardation syndrome HDAC4 1363 605314 2, 4, 7, 8 Brachydactyly-syndactyly syndrome HOXD13 1975 142989 2, 4, 10, 11 Branchiooculofacial syndrome TFAP2A 2509 107580 2, 4, 7, 8 C syndrome CD96 1839 606037 2, 3, 4, 7, 8, 10, 11 Campomelic dysplasia SOX9 1218 608160 2, 4, 10, 11 Camptodactyly-arthropathy-coxa vara-pericarditis syndrome PRG4 2524 604283 2, 3, 4, 10, 11 Camurati-Engelmann disease TGFB1 293 190180 2, 4 Cantu syndrome ABCC9 1082 601439 2, 3, 4, 7, 8, 10, 11 Carpenter syndrome RAB23 2423 606144 2, 3, 4, 10, 11 Carpenter syndrome type 2 MEGF8 2422 604267 2, 3, 4, 7, 8, 10, 11 Cartilage-hair hypoplasia RMRP 2083 157660 1, 2, 4, 10, 11 Central hypoventilation syndrome with or without Hirschsprung disease PHOX2B 740 603851 2, 3, 4, 10, 11, 12 Central hypoventilation syndrome, congenital ASCL1 712 100790 2, 4, 10, 11 Central hypoventilation syndrome, congenital BDNF 1494 113505 2, 4, 10, 11 Central hypoventilation syndrome, congenital ECE1 1497 600423 2, 4, 7, 8

☐ 1-Hotspot Testing ☐ 2-Carrier Testing (point mutation) ☐ 3-Carrier Testing (del/dup) ☐ 4-Full Gene Sequencing (Sanger) ☐ 5-NGS Panel ☐ 6-NGS Panel + CNV ☐ 7-NGS Panel Plus ☐ 8-NGS Panel Plus + CNV ☐ 9-NGS Panel Genomic ☐ 10-Deletion/Duplication with qPCR/MLPA ☐ 11-Sequencing + Deletion/Duplication ☐ 12-Repeat Expansions ☐ 13-Somatic Mutation Analysis ☐ 14-Biochemical Enzyme Analysis ☐ 15-Biomarker Analysis Page 93 ☐ Biochemical Enzyme Panel ☐ Biochemical Genetics Panel Plus V72.1_July2018 Test x Disease Gene OMIM Gene Available test methods code Seckel syndrome type 5 CEP152 1077 613529 2, 4, 7, 8 Seckel syndrome type 6 CEP63 738 614724 2, 4, 7, 8 Seckel syndrome type 7 NIN 2636 608684 2, 4, 7, 8 SED congenita COL2A1 943 120140 2, 4, 7, 8, 10, 11 Seizures, scoliosis, and macrocephaly syndrome EXT2 2375 608210 2, 4, 7, 8, 10, 11 Septooptic dysplasia HESX1 1265 601802 2, 4, 10, 11 SERKAL syndrome WNT4 122 603490 2, 4, 10, 11 Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity NHEJ1 1211 611290 2, 3, 4, 10, 11 to ionizing radiation Short stature syndrome SHOX 1360 312865 2, 4, 10, 11 Short stature, microcephaly, and endocrine dysfunction XRCC4 2798 194363 2, 3, 4, 10, 11 Short stature, optic nerve atrophy, and Pelger-Huet anomaly NBAS 2605 608025 2, 4, 7, 8 SHORT syndrome PIK3R1 2523 171833 2, 4, 7, 8 Short-rib thoracic dysplasia type 2 with or without polydactyly IFT80 2440 611177 2, 4, 7, 8 Short-rib thoracic dysplasia type 3 with or without polydactyly DYNC2H1 2438 603297 2, 3, 7, 8, 10 Short-rib thoracic dysplasia type 4 with or without polydactyly TTC21B 2001 612014 2, 3, 4, 7, 8, 10, 11 Short-rib thoracic dysplasia type 5 with or without polydactyly WDR19 2424 608151 2, 4, 7, 8 Short-rib thoracic dysplasia type 6 with or without polydactyly NEK1 1984 604588 2, 4, 7, 8 Short-rib thoracic dysplasia type 7 with or without polydactyly WDR35 2425 613602 2, 4, 7, 8 Short-rib thoracic dysplasia type 8 with or without polydactyly WDR60 2444 615462 2, 4, 7, 8 Short-rib thoracic dysplasia type 10 with or without polydactyly IFT172 2441 607386 2, 4, 7, 8 Short-rib thoracic dysplasia type 11 with or without polydactyly WDR34 2442 613363 2, 4 Shprintzen-Goldberg syndrome SKI 88 164780 2, 3, 4, 10, 11 Silver-Russell syndrome chr. 11p15 92 10 maternal Silver-Russell syndrome 2933 10 UPD chr. 7 Skeletal abnormalities, CBFB related CBFB 1996 121360 2, 4 SMED Strudwick type COL2A1 943 120140 2, 4, 7, 8, 10, 11 Smith-Lemli-Opitz syndrome DHCR7 1809 602858 2, 4, 10, 11 Sotos syndrome type 1 NSD1 201 606681 2, 4, 7, 8, 10, 11 Sotos-like syndrome NFIX 1277 164005 2, 3, 4, 7, 8, 10, 11 Speech-language disorder type 1 FOXP2 1266 605317 2, 3, 4, 7, 8, 10, 11 Spina bifida folate sensitive MTRR 982 602568 2, 4, 7, 8 Split-hand/foot malformation type 1 with sensorineural hearing loss DLX5 2249 600028 2, 3, 4, 10, 11 Split-hand/foot malformation type 6 WNT10B 2250 601906 2, 3, 4, 10, 11 Spondylocostal dysostosis type 5 TBX6 2802 602427 2, 4 Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures B3GALT6 3056 615291 2, 4 Spondylo-megaepiphyseal-metaphyseal dysplasia NKX3-2 2085 602183 2, 4, 10, 11 Spondyloperipheral dysplasia COL2A1 943 120140 2, 4, 7, 8, 10, 11 Stiff skin syndrome FBN1 950 134797 2, 7, 8, 10 Stuve-Wiedemann syndrome LIFR 1267 151443 2, 3, 4, 7, 8, 10, 11 Syndactyly type 1 HOXD13 1975 142989 2, 4, 10, 11 Syndactyly type 5 HOXD13 1975 142989 2, 4, 10, 11 Syndactyly, mesoaxial synostotic, with phalangeal reduction BHLHA9 2968 615416 2, 4, 10, 11 TANC2 related brain disorders TANC2 1943 615047 2, 4, 7, 8 maternal Temple syndrome 2934 10 UPD chr. 14 Temple-Baraitser syndrome KCNH1 2792 603305 2, 4, 7, 8 Temtamy syndrome C12orf57 2129 615140 2, 4 Tetraamelia, autosomal recessive WNT3 1268 165330 2, 4 Three M syndrome type 1 CUL7 1269 609577 2, 3, 4, 7, 8, 10, 11 Three M syndrome type 2 OBSL1 1952 610991 2, 3, 4, 7, 8, 10, 11 Three M syndrome type 3 CCDC8 2468 614145 2, 4 Toe syndactyly, telecanthus, and anogenital and renal malformations FAM58A 1270 300708 2, 4 Tooth agenesis, selective type 1 MSX1 170 142983 2, 4, 10, 11 Tooth agenesis, selective type 3 PAX9 1205 167416 2, 3, 4, 10, 11 Townes-Brocks syndrome SALL1 1271 602218 2, 3, 4, 10, 11 Transposition of great arteries, dextro-looped 3 GDF1 2040 602880 2, 3, 4, 10, 11 Transposition of the great arteries, dextro-looped 1 MED13L 2912 608771 2, 4, 7, 8 Treacher Collins syndrome type 1 TCOF1 2130 606847 2, 4, 7, 8, 10, 11 Treacher Collins syndrome type 2 POLR1D 2178 613715 2, 4, 10, 11 Treacher Collins syndrome type 3 POLR1C 2179 610060 2, 4 Trigonocephaly type 1 FGFR1 1136 136350 2, 4, 10, 11 Ulna and fibula, absence of, with severe limb deficiency WNT7A 327 601570 2, 3, 4, 10, 11 Ulnar-Mammary syndrome TBX3 1272 601621 2, 3, 4, 10, 11 Urofacial syndrome LRIG2 1524 608869 2, 4, 7, 8 ☐ 1-Hotspot Testing ☐ 2-Carrier Testing (point mutation) ☐ 3-Carrier Testing (del/dup) ☐ 4-Full Gene Sequencing (Sanger) ☐ 5-NGS Panel ☐ 6-NGS Panel + CNV ☐ 7-NGS Panel Plus ☐ 8-NGS Panel Plus + CNV ☐ 9-NGS Panel Genomic ☐ 10-Deletion/Duplication with qPCR/MLPA ☐ 11-Sequencing + Deletion/Duplication ☐ 12-Repeat Expansions Page 94 ☐ 13-Somatic Mutation Analysis ☐ 14-Biochemical Enzyme Analysis ☐ 15-Biomarker Analysis V72.1_July2018 ☐ Biochemical Enzyme Panel ☐ Biochemical Genetics Panel Plus Test x Disease Gene OMIM Gene Available test methods code Van den Ende-Gupta syndrome SCARF2 1882 613619 2, 4, 7, 8 van der Woude syndrome type 1 IRF6 2826 607199 2, 4, 10, 11 van der Woude syndrome type 2 GRHL3 1892 608317 2, 4 Van Maldergem syndrome type 2 FAT4 2580 612411 2, 4, 7, 8 Vater association HOXD13 1975 142989 2, 4, 10, 11 Vici syndrome EPG5 2090 615068 2, 3, 4, 7, 8, 10, 11 Visceral myopathy ACTG2 2882 102545 2, 3, 4, 10, 11 Warburg micro syndrome type 1 RAB3GAP1 237 602536 2, 3, 4, 7, 8, 10, 11 Warburg micro syndrome type 2 RAB3GAP2 1619 609275 2, 3, 4, 7, 8, 10, 11 Warsaw breakage syndrome DDX11 2690 601150 2, 4, 7, 8 Weaver syndrome EZH2 1872 601573 2, 3, 4, 7, 8, 10, 11 Webb-Dattani syndrome ARNT2 2781 606036 2, 4, 7, 8 Weill-Marchesani syndrome type 3 LTBP2 887 602091 2, 4, 7, 8 Weill-Marchesani syndrome, dominant type 2 FBN1 950 134797 2, 7, 8, 10 Werner syndrome WRN 2545 604611 2, 3, 4, 7, 8, 10, 11 Wiedemann-Steiner syndrome KMT2A 1432 159555 2, 3, 4, 7, 8, 10, 11 Williams-Beuren syndrome chr. 7q11.23 2760 10 Witkop syndrome MSX1 170 142983 2, 4, 10, 11 XFE progeroid syndrome ERCC4 2543 133520 2, 4, 7, 8 ZIC5 related brain disorders ZIC5 2199 2, 4

Deletion / duplication testing Test x Panel name Genes Available test methods (genes analyzed) code BRCA1, BRCA2 panel BRCA1, BRCA2 BRCA1, BRCA2 5046 7, 10 BRCA1, BRCA2 somatic mutation analysis BRCA1, BRCA2 42005 136 ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH2, BRIP1, RAD51D, CHEK2, MEN1, MLH1, MRE11A, MSH2, MSH6, RAD50, RAD51C, PMS2, BRCA2, Breast ovarian cancer panel MUTYH, NBN, PALB2, PMS1, PMS2, PTEN, PALB2, MSH6, MEN1, MLH1, ATM, 5228 5, 6 RAD50, RAD51C, RAD51D, STK11, TP53, BRCA1, MUTYH, STK11, TP53, XRCC2 PTEN, CDH1 ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CentoBreast® panel CHEK2, NBN, PALB2, PTEN, RAD51C, STK11, 5264 5, 6 TP53 APC, ATM, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, FH, FLCN, HNF1A, HNF1B, HOXB13, MC1R, MEN1, MET, MITF, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, NTHL1, PALB2, CentoCancer panel 5296 5, 6 PMS1, PMS2, POLD1, POLE, POT1, PRSS1, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, TSC1, TSC2, VHL, WT1, XRCC2, XRCC3 APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, CentoColon extended panel MSH2, MSH6, MUTYH, NTHL1, PMS2, POLD1, 5297 5, 6 POLE, PTEN, SMAD4, STK11, TP53 MSH2, EPCAM, MSH6, MLH1, Colon cancer non-polyposis panel MSH2, MLH1, MSH6, PMS2, EPCAM 5230 5, 6 PMS2 STK11, APC, PTEN, SMAD4, Colon cancer with polyps panel APC, BMPR1A, MUTYH, PTEN, SMAD4, STK11 5231 5, 6 MUTYH, BMPR1A BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH6, MSH2, EPCAM, MSH6, MLH1, Gastric cancer panel, targeted 5233 5, 6 PMS1, PMS2, SMAD4 SMAD4, CDH1, BMPR1A, PMS2 SDHA, VHL, SDHD, SDHAF2, Multiple endocrine neoplasias /paragangli- CDKN1B, MAX, MEN1, RET, SDHA, SDHAF2, MAX, CDKN1B, MEN1, SDHB, 5276 5, 6 oma/pheochromocytoma panel SDHB, SDHC, SDHD, TMEM127, VHL SDHC, RET ASXL1, CEBPA, DNMT3A, ETV6, EZH2, IDH1, IDH2, KIT, KRAS, NPM1, NRAS, PTPN11, Myeloid Tumor Panel 42003 136 RAD21, RUNX1, SF3B1, SMC1A, SMC3, STAG2, TET2, TP53, U2AF1, WT1 MSH2, BRIP1, RAD51D, RAD50, BARD1, BRCA1, BRCA2, BRIP1, EPCAM, MLH1, RAD51C, PMS2, BRCA2, STK11, Ovarian cancer panel, targeted MRE11A, MSH2, MSH6, NBN, PMS1, PMS2, 5232 5, 6 EPCAM, TP53, MSH6, MLH1, RAD50, RAD51C, RAD51D, STK11, TP53 BRCA1 CDKN2A, MSH2, BMPR1A, PMS2, APC, ATM, BMPR1A, CDKN2A, EPCAM, MLH1, STK11, PALB2, EPCAM, APC, Pancreatic cancer panel, targeted MSH2, MSH6, PALB2, PMS1, PMS2, PRSS1, 5234 5, 6 PRSS1, MSH6, SMAD4, MLH1, SMAD4, STK11 ATM GDNF, KIF1B, MAX, MEN1, NF1, RET, SDHA, GDNF, MAX, MEN1, NF1, RET, PGL / PCC / GIST panel, targeted SDHAF2, SDHB, SDHC, SDHD, TMEM127, SDHA, SDHAF2, SDHB, SDHC, 5239 5, 6 TP53, VHL SDHD, TP53, VHL BRCA1, BRCA2, CHEK2, HOXB13, MLH1, CHEK2, MSH2, BRCA2, TP53, Prostate cancer panel 5281 5, 6 MSH2, MSH6, NBN, PTEN, TP53 PTEN, MSH6, MLH1, BRCA1 MSH2, TSC1, TSC2, WT1, MITF, EPCAM, FH, FLCN, HNF1A, HNF1B, MET, MITF, PMS2, FH, SDHD, VHL, FLCN, Renal cancer panel, targeted MLH1, MSH2, MSH6, PMS1, PMS2, PTEN, 5235 5, 6 EPCAM, HNF1A, PTEN, HNF1B, SDHB, SDHD, TSC1, TSC2, VHL, WT1 MSH6, MLH1, MET, SDHB CDKN2A, EPCAM, MC1R, MITF, MLH1, MSH2, MSH2, CDKN2A, EPCAM, PTCH1, Skin cancer panel, targeted 5236 5, 6 MSH6, PMS1, PMS2, POT1, PTCH1, XRCC3 MSH6, MLH1, MITF, PMS2 Thyroid cancer panel, targeted APC, PTEN, RET APC, PTEN, RET 5237 5, 6 EPCAM, MLH1, MSH2, MSH6, PMS1, PMS2, MSH2, EPCAM, PTEN, MSH6, Uterine cancer panel, targeted 5238 5, 6 PTEN MLH1, PMS2

Test x Disease Gene OMIM Gene Available test methods code Acute myeloid leukemia, somatic, DNMT3A related DNMT3A 30014 602769 2, 13 Basal cell nevus syndrome PTCH1 1216 601309 2, 4, 7, 8, 10, 11 Basal cell nevus syndrome SUFU 2360 607035 2, 3, 4, 7, 8, 10, 11 Basal cell nevus syndrome due to germline PTCH2 mutation PTCH2 2687 603673 2, 4, 7, 8 Beckwith-Wiedemann syndrome CDKN1C 1164 600856 2, 4, 10, 11 Beckwith-Wiedemann syndrome chr. 11p15 92 10 Beckwith-Wiedemann syndrome H19 1750 103280 2, 4, 10, 11 Beckwith-Wiedemann syndrome KCNQ1OT1 1749 604115 10 Beckwith-Wiedemann syndrome NSD1 201 606681 2, 4, 7, 8, 10, 11 BRAF somatic Hotspot: c.1799T>A p.V600E BRAF 46008 164757 1 BRAF, selective sequencing of exon 15 BRAF 45013 164757 1 Breast cancer, male, susceptibility to BRCA2 379 600185 2, 4, 7, 10, 11 Breast cancer, RINT1 related RINT1 2626 610089 2, 4, 7, 8 Breast cancer, susceptibility to BARD1 986 601593 2, 4, 7, 8 Breast cancer, susceptibility to PALB2 388 610355 2, 4, 7, 8, 10, 11 Breast cancer, susceptibility to RECQL 3060 600537 2, 4 Breast cancer, susceptibility to XRCC3 2332 600675 2, 4 Breast-ovarian cancer BRCA1 1165 113705 1, 2, 4, 7, 10, 11 Breast-ovarian cancer RAD51C 1167 602774 2, 4, 10, 11 Breast-ovarian cancer, familial, susceptibility to, type 4 RAD51D 1168 602954 2, 4, 10, 11 Breast-ovarian cancer, familial, type 2 BRCA2 379 600185 1, 2, 4, 7, 10, 11 CALR, selective sequencing of exon 9 CALR 45019 109091 1 Carcinoid tumors, intestinal SDHD 1190 602690 2, 4, 10, 11 Carney complex type 1 PRKAR1A 1192 188830 2, 3, 4, 10, 11 Cell cycle disorder, CDC20 related CDC20 2478 603618 2, 4 Colorectal cancer, hereditary NRAS 1248 164790 2, 4 Colorectal cancer, hereditary nonpolyposis type 1 MSH2 1170 609309 2, 4, 7, 8, 10, 11 Colorectal cancer, hereditary nonpolyposis type 2 MLH1 1171 120436 2, 4, 7, 8, 10, 11 Colorectal cancer, hereditary nonpolyposis type 4 PMS2 1172 600259 2, 4, 10, 11 Colorectal cancer, hereditary nonpolyposis type 5 MSH6 1173 600678 2, 4, 7, 8, 10, 11 Colorectal cancer, hereditary nonpolyposis type 6 TGFBR2 295 190182 2, 4, 7, 8, 10, 11 Colorectal cancer, hereditary nonpolyposis type 7 MLH3 1174 604395 2, 4, 7, 8 Colorectal cancer, hereditary nonpolyposis type 8 EPCAM 1175 185535 2, 4, 10, 11 Colorectal cancer, hereditary, susceptibility to CCND1 2134 168461 2, 4, 10, 11 Cowden syndrome type 1 PTEN 1176 601728 2, 4, 10, 11 Cowden syndrome type 3 SDHD 1190 602690 2, 4, 10, 11 Cowden syndrome type 5 PIK3CA 917 171834 2, 3, 4, 10, 11 Cowden syndrome type 6 AKT1 1832 164730 2, 3, 4, 7, 8, 10, 11 Cutaneous telangiectasia and cancer syndrome, familial ATR 1851 601215 2, 7, 8 Cylindromatosis, familial CYLD 2541 605018 2, 3, 4, 7, 8, 10, 11 Desmoid disease, hereditary APC 1163 611731 2, 4, 7, 8, 10, 11 EGFR somatic Hotspot: c.2573T>G, p.L858R EGFR 46003 131550 1 EGFR, selective sequencing of exons 18-21 EGFR 45017 131550 1 Endometrial cancer, familial, MSH6 related MSH6 1173 600678 2, 4, 7, 8, 10, 11 Familial adenomatous polyposis coli APC 1163 611731 2, 4, 7, 8, 10, 11 Familial adenomatous polyposis type 2 MUTYH 1169 604933 2, 4, 7, 8, 10, 11 Familial adenomatous polyposis type 3 NTHL1 2874 602656 2, 3, 4, 10, 11 Familial adenomatous polyposis type 4 MSH3 56 600887 2, 3, 4, 7, 8, 10, 11 Gastric cancer, hereditary diffuse CDH1 1177 192090 2, 4, 7, 8, 10, 11 Gastrointestinal stromal tumor, familial KIT 1178 164920 2, 4, 7, 8, 10, 11 Glioblastoma type 3, susceptibility to, due to BRCA2 germline mutation BRCA2 379 600185 2, 4, 7, 10, 11 Granulomatous disease, chronic, autosomal recessive, cytochrome b- positive, type 1 NCF1 1968 608512 2, 3, 4, 7, 8, 10, 11 Hemangioma capillary infantile ANTXR1 1707 606410 2, 3, 4, 7, 8, 10, 11 Hemangioma, capillary infantile, familial, susceptibility to KDR 2141 191306 2, 4, 7, 8 Hereditary breast and ovarian cancer syndrome, RAD50 related RAD50 2321 604040 2, 4, 7, 8, 10, 11 Hereditary Retinoblastoma RB1 1643 614041 2, 4, 7, 8, 10, 11 Hurthle cell thyroid carcinoma, due to germline NDUFA13 mutation NDUFA13 40 609435 2, 4 IDH1, selective sequencing of exon 4 IDH1 45015 147700 1 IDH2, selective sequencing of exon 4 IDH2 45016 147650 1 JAK2, selective sequencing of exons 12, 14 and 16 JAK2 45014 147796 1 Juvenile myelomonocytic leukemia, due to CBL germline mutation CBL 115 165360 2, 3, 4, 7, 8, 10, 11 Juvenile polyposis syndrome BMPR1A 1179 601299 2, 4, 10, 11

› Sample size: 20mg › Sample size: 3-5ml › Sample size: 50µl of EDTA blood per › For newborns and small children circle (circles completely saturated) › Fresh frozen tissue shipped on dry ice › 10-20 filled in circles, depending on the 2ml is sufficient › Paraffin embedded tissue – 25-50mg of › Please note: when ordering type of analysis ordered tissue or 5-10 micron sections (thick) in a more than one panel, please › Please note: when ordering more than sterile tube contact CENTOGENE for exact one or a large panel, please contact requirements on final blood-EDTA CENTOGENE for exact requirements on number of CentoCard®s. volume Somatic Genomics › 5-10µm with marked area of enriched tumor or tissue parraffin block for macrodissection (min. 50mg of tissue) › Pathology report EDTA tube Filtercard › Fixation type accepted: 10% Formalin or 4% Paraformaldehyde or Frozen tissue from OCT-Cell blocks - Fresh Frozen Please do not send tissue fixed in Bouins › Sample size: 10ml › Sample size: 10 villi or gluteraldehyde. Ship in a sterile tube at room temperature - no cold pack required. › Clear – no blood contamination › Cleaned in RPMI media with fetal calf serum (FCS) Tissue sample Amniotic fluid Chorionic villi

› Sample size: 3-5ml

› Sample size: 5µg (20µg in case of › Sample size: 10ml of blood › Please note: when ordering more NGS panels) shipped in cell-free DNA BCT than one panel, please contact STRECK tubes. Blood should not CENTOGENE for exact requirement › We accept purified DNA with a ratio contain any other anti-coagulants of sample volume of absorbance at 260 and 280nm or preservatives as this may cause (A260/280) in the range from coagulation. 1.6 - 2.1.

Purified DNA ctDNA Cord blood

Sample transport Filtercards, EDTA blood, cord blood & saliva: Samples can be sent via regular mail at room temperature. Liquid blood is stable for up to 4 days during transport. Amniotic fluid: Min. 10ml samples placed into a sterile conical tube. These should be shipped overnight at room temperature. Care must be given that the samples do not freeze. Chorionic villi, and any tissue samples: These specimens need to be shipped in a minimum of 35ml of RPMI transport medium with fetal calf serum at room temperature. The samples must be shipped in a manner to secure that the samples do not freeze (not below +4°C) especially during winter months. Blood for ctDNA analysis: Blood sample must be sent in the glass STRECK tubes as per manufacturer’s recommendation. Samples must be shipped immediately after sampling and at no stage should be frozen. Blood samples collected in STRECK tubes can be shipped at room temperature as they are stable upto 14 days. Samples in glass STRECK tubes must be handled and shipped carefully to prevent any damage of the glass tubes during shipment.

Rejection of sample All samples that are received without proper identification and where there is no possibility to correctly identify the specimen, have to be rejected. The referring physician will be notified and a new sample will need to be collected. In the case that no test is ordered or the order is unclear, we will accept a written order from the referring physician with a signed requisition.

Page 100 V72.1_July2018 Specific material requirements for somatic and hereditary oncogenetic analyses

HEREDITARY CANCER PANELS

› 1 ml EDTA Blood › 1 filtercard › 2-4 µg DNA (please refer to www.centogene.com for individual panel requirements)

SOMATIC MYELOID TUMOR PANEL

› 1-3 ml Bone marrow sample › 1ml EDTA Blood › 1µg DNA isolated from either bone marrow or blood

SOMATIC SOLID TUMOR PANELS, SINGLE GENE AND POINT MUTATION ANALYSIS (mandatory requirement)

› 10 FFPE sections of 5-10µm thickness with a pathology report and areas on the slides marked clearly with enriched tumor (no fresh frozen material) › 1µg DNA from tumor-enriched section › 1ml EDTA Blood or 1µg DNA from normal tissue (for eg. from buccal swab) as a recommended control › Year of tissue fixation › Tumor grading, stage › Protocol of tissue fixation, if available › Oncology report in case of a relapse testing › Tissue of origin

› Contact Details Please send your sample and the requisition form to: Phone: +49 (0) 381 80 113 - 416 Fax: +49 (0) 381 80 113 - 401 CENTOGENE AG [email protected] Am Strande 7 www.centogene.com 18055 Rostock, Germany

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