Hereditary Cancer. Genetic Testing Services. The GeneDx Experience

Transcription

1 Hereditary Cancer Genetic Testing Services The GeneDx Experience

2 GeneDx: Where Rare is Common In medical school there is a saying, When you hear hoofbeats, think horses not zebras. Think of common causes of the symptoms first, not the rare. When you encounter a zebra, think GeneDx. We specialize in diagnosing rare genetic disorders. From Humble Beginnings to Industry Leaders Sherri Bale and John Compton were working on identifying genetic causes for various rare disorders at the National Institutes of Health (NIH). Families were requesting clinical diagnoses, but they could not provide that service through a research laboratory. Other commercial labs did not want to test for these disorders because of such low volume. To meet that need, Sherri and John decided to open a lab in the year 2000 to offer testing for these rare and ultra-rare disorders. Today, GeneDx provides genetic testing for hundreds of genetic disorders utilizing cutting-edge technologies and offers a broad array of special services such as: carrier screening, targeted testing, prenatal diagnosis, research testing, and exome and genome sequencing. Sherri and John have been recognized for their great work numerous times. Sherri is a member of various working groups with the American College of Medical Genetics, and works closely with the Association for Molecular Pathology in the projects related to genetic testing. 2000: Company founded with 10 tests 2007: Launched Array CGH 2011: Launched Neurology Panels and XomeDx 2013: Launched Hereditary Cancer Panels 2015: Acquired by OPKO Health 2006: Acquired by BRLI 2008: Launched Cardiology Panels 2015: Launched XomeDxXpress 2017: Launched GenomeSeqDx 1

3 GeneDx Expertise Clinical Expertise 150+ MDs/PhDs 140+ Genetic Counselors 500+ Publications/Abstracts 35+ Geneticists Technical Experience 18 years: Sanger Sequencing 200,000+ tests performed 11 years: Microarrays 240,000+ tests performed 10 years: Next-Generation Sequencing 230,000+ tests performed 7 years: Whole Exome Sequencing 72,000+ exomes sequenced Sherri Bale, PhD, FACMG, our founder, is a co-author on the 2007 and 2015 guidelines on the interpretation of sequence variants. 1,2 She is also a co-author on the 2013 ACMG guidelines on next-generation sequencing ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee. Genet Med Apr;10(4): (PMID: ) 2. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL. ACMG Laboratory Quality Assurance Committee. Genet Med May;17(5): (PMID: ) 3. ACMG clinical laboratory standards for next-generation sequencing. Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, Friez MJ, Funke BH, Hegde MR, Lyon E; Working Group of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee. Genet Med Sep;15(9): (PMID: ) 2

4 Our Cancer Panels at a Glance GeneDx offers a comprehensive testing menu which includes clinically relevant genes associated with hereditary cancer and meets the testing needs across clinical indications. Breast and Gynecologic Cancer Panels (see pages 5 and 6) BRCA1/BRCA2 Ashkenazi Founder Panel (TAT 8-10 days) Three Targeted Pathogenic Variants BRCA1/BRCA2 Sequencing and Deletion/Duplication Analysis (TAT 8-10 days) Breast Cancer Management Panel (TAT 2 weeks; RUSH surgical cases 8-10 days) 9 genes Breast/Gyn Cancer Panel (TAT 2 weeks) 23 genes Colorectal Cancer Panels (see pages 7 and 8) Colorectal Cancer Panel (TAT 2 weeks) 20 genes Lynch/Colorectal High Risk Panel (TAT 2 weeks) 7 genes Panels for Multiple Cancer Types (see page 9) Comprehensive Common Cancer Panel (TAT 2 weeks) 46 genes Common Cancer Management Panel (TAT 2 weeks) 37 genes Tumor Specific Panels (see page 9) Melanoma Panel (TAT 2 weeks) 9 genes Pancreatic Cancer Panel (TAT 2 weeks) 15 genes Pediatric Tumor Panel (TAT 3 weeks) 27 genes PGL/PCC Panel (TAT 3 weeks) 12 genes Hereditary Prostate Cancer Panel (TAT 2 weeks) 12 genes Renal Cancer Panel (TAT 3 weeks) 18 genes Custom Panel (see page 10) 3 OncoGeneDx Custom Panel (TAT 3 weeks) up to 64 genes

5 Hereditary Cancer Testing at GeneDx Experience Matters: Over 140,000 Hereditary Cancer Tests Performed Tumor Specific Panels 8% Custom Panels 11% Breast and Gynecologic Cancer Panels 52% Panels for Multiple Cancer Types 25% Colorectal and Lynch Syndrome Related Cancer Panels 4% GeneDx Offers a Comprehensive Cancer Program Identification Education Selection Support GeneDx offers tools to assist providers in identifying individuals who may be at risk to develop cancer due to a hereditary cancer syndrome GeneDx provides educational materials to improve the understanding of hereditary cancer and genetic testing GeneDx offers a comprehensive and flexible testing menu to meet the testing needs of health care providers and their patients GeneDx offers a variety of post-test patient educational and management tools 4

6 Hereditary Breast and Gynecologic Cancer Testing Approximately 5-10% of all breast cancers, 25% of all ovarian cancers, and 5-10% of all endometrial cancers occur because a woman was born with a pathogenic variant in a gene that increased her risk to develop cancer. Identifying Patients at Risk for Hereditary Breast and Gynecologic Cancer Breast or endometrial cancer diagnosed under 50 years of age Multiple cancers in one person, either of the same origin (such as two separate breast cancers) or of different origins (such as breast and ovarian cancer or endometrial and colon cancer) Ovarian cancer or male breast cancer at any age Multiple relatives diagnosed with the same or related cancers (including breast, ovarian, endometrial, pancreatic and/or prostate) on the same side of the family and spanning multiple generations Ashkenazi Jewish ancestry with a history of breast, ovarian or pancreatic cancer A known pathogenic variant in a blood relative Exploring the Positive Results at GeneDx for Breast Cancer Pathogenic/likely pathogenic variants have been found in a number of genes in women with a personal history of breast cancer. The pie chart below describes our experience at GeneDx. Pathogenic and Likely Pathogenic Variants in Women with Breast Cancer Other Moderate-Risk Genes** 6% ATM 12% Newer-Risk Genes*** 7% BRCA1 16% High-Risk Genes Moderate-Risk Genes Newer-Risk Genes BRCA2 19% CHEK2 26% Other High Risk Genes* 5% PALB2 9% *Other High-Risk Genes: CDH1, MLH1, MSH2, MSH6, PMS2, PTEN, TP53 **Other Moderate-Risk Genes: BRIP1, RAD51C, RAD51D ***Newer-Risk Genes: FANCC, NBN, BARD1 5

7 Hereditary Breast and Gynecologic Cancer Panels Breast and Ovarian Cancer Testing Options BRCA1/BRCA2 Ashkenazi Founder Panel (TAT 8-10 days) Targeted testing for three known founder variants in BRCA1 and BRCA2 BRCA1/BRCA2 Sequencing and Deletion/Duplication Analysis (TAT 8-10 days) BRCA1, BRCA2 Breast Cancer Management Panel (TAT 2 weeks; RUSH surgical cases 8-10 days) ATM, BRCA1, BRCA2, CDH1, CHEK2, NBN, PALB2, PTEN, TP53 Breast/Gyn Cancer Panel (TAT 2 weeks) ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FANCC, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, POLD1, PTEN, RAD51C, RAD51D, RECQL, TP53 Endometrial Cancer Testing Options Breast/Gyn Cancer Panel (TAT 2 weeks) ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FANCC, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, POLD1, PTEN, RAD51C, RAD51D, RECQL, TP53 Lynch/Colorectal High Risk Panel (TAT 2 weeks) APC, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2 For patients and families with a history of rare or multiple cancer types, we also offer more comprehensive hereditary cancer testing options. Please see pages 9 and 10 for more details. Positive Yields for Patients Referred for Hereditary Breast and Gynecologic Cancer Testing Female Breast 9.6% Female Breast, Personal and Family History Female Breast Cancer Diagnosed <50 9.8% 10.8% Ovarian 13.1% Endometrial 9.2% Male Breast 15.4% 0% 2% 4% 6% 8% 10% 12% 14% 16% 6

8 Hereditary Colorectal Cancer Testing Pathogenic variants in several genes have been associated with hereditary colorectal cancer, such as Lynch and other cancer syndromes. Individuals with pathogenic variants in these genes may develop colorectal cancer at young ages or may have an increased risk for multiple cancer diagnoses in a lifetime. Identifying Patients at Risk for Hereditary Colorectal Cancer Colorectal or endometrial cancer under 50 years of age Multiple cancers in one person, either of the same origin (such as two separate colon cancers) or of different origins (such as colorectal and endometrial cancer) Diagnosis of multiple colon polyps at any age Tumor testing which indicates an increased risk for Lynch syndrome Multiple relatives diagnosed with the same or related cancers (such as colorectal, endometrial, ovarian, urinary tract, gastric) on the same side of the family and spanning multiple generations A known pathogenic variant in a blood relative Exploring the Results at GeneDx for Colorectal Cancer Pathogenic/likely pathogenic variants have been found in a number of genes in patients with a personal history of colorectal cancer. The pie chart below describes our experience at GeneDx. Pathogenic and Likely Pathogenic Variants in Individuals with Colorectal Cancer MLH1 22% Other Cancer Genes** 9% MSH2 16% ATM 4% CHEK2 7% Other Polyp Genes* 2% APC 7% MUTYH 11% PMS2 11% MSH6 10% Lynch Genes Polyp Genes Other Inherited Cancer Genes EPCAM-related 1% *Other Polyp Genes: BMPR1A, POLE, PTEN, STK11 **Other Cancer Genes: AXIN2, BARD1, BRCA1, BRCA2, BRIP1, FANCC, NBN, PALB2, RAD51C, RAD51D, TP53, SDHD 7

9 Hereditary Colorectal Cancer Panels Colorectal Cancer Testing Options Lynch/Colorectal High Risk Panel (TAT 2 weeks) APC, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2 Colorectal Cancer Panel (TAT 2 weeks) APC, ATM, AXIN2, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NTHL1, PMS2, POLD1, POLE, PTEN, SCG5/GREM1, SMAD4, STK11, TP53 For patients and families with a history of rare or multiple cancer types, we also offer more comprehensive hereditary cancer testing options. Please see pages 9 and 10 for more details. Positive Yields Among Patients with Lynch-Related Cancers Colorectal 14.5% Endometrial 13.6% Ovarian 12.3% Gastric 14.1% 0% 2% 4% 6% 8% 10% 12% 14% 16% 18% 8

10 Testing for Multiple Cancer Types In some cases, it may be beneficial to address a broad range of cancer susceptibility genes. Testing using these panels may be appropriate for patients/families with a wide spectrum of cancers or for providers who want to customize their cancer panel. Panels for Multiple Cancer Types Comprehensive Common Cancer Panel (TAT 2 weeks) APC, ATM, AXIN2, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, FANCC, FH, FLCN, HOXB13, MET, MITF, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PMS2, POLD1, POLE, POT1, PTEN, RAD51C, RAD51D, RECQL, SCG5/GREM1, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, TSC1, TSC2, VHL Common Cancer Management Panel (TAT 2 weeks) APC, ATM, AXIN2, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDKN2A, CHEK2, EPCAM, FH, FLCN, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SCG5/ GREM1, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, TSC1, TSC2, VHL OncoGeneDx Custom Panel (TAT 3 weeks) Create a customized cancer panel from a list of 64 cancer susceptibility genes. Please see page 10 for more details. GeneDx offers a variety of testing options that may be appropriate for patients with a personal or family history of a rare or specific cancer phenotype(s). Tumor Specific Panels Melanoma Panel (TAT 2 weeks) BAP1, BRCA2, CDK4, CDKN2A, MITF, POT1, PTEN, RB1, TP53 Pancreatic Cancer Panel (TAT 2 weeks) APC, ATM, BRCA1, BRCA2, CDK4, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, TP53, VHL Pediatric Tumor Panel (TAT 3 weeks) ALK, APC, CDC73, DICER1, EPCAM, MEN1, MLH1, MSH2, MSH6, NF1, NF2, PHOX2B, PMS2, PRKAR1A, PTCH1, PTEN,RB1, RET, SMARCA4, SMARCB1, STK11, SUFU, TP53, TSC1, TSC2, VHL, WT1 PGL/PCC Panel (TAT 3 weeks) FH, MAX, MEN1, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL Hereditary Prostate Cancer Panel (TAT 2 weeks) ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PMS2, TP53 Renal Cancer Panel (TAT 3 weeks) BAP1, EPCAM, FH, FLCN, MET, MITF, MLH1, MSH2, MSH6, PMS2, PTEN, SDHB, SDHC, SDHD, TP53, TSC1, TSC2, VHL 9

11 Testing with a Custom Panel OncoGeneDx Custom Panel The OncoGeneDx Custom Panel is a flexible testing option that allows providers to customize their test in order to meet the individual needs of their patient. Providers have the option to choose anywhere from a single gene test to a full 64 gene panel. Below is a list of available genes separated into their current risk category. High-Risk Genes Well-studied Greater than 4-fold risk of developing one or more cancers Can cause a moderate risk for other cancers National or expert opinion guidelines for screening and prevention are established Moderate-Risk Genes Well-studied Approximately 2- to 4-fold risk of developing one or more cancers May increase risk for other cancers Limited guidelines for screening and prevention Newer-Risk Genes Not as well-studied Precise lifetime risks and tumor spectrum not yet determined Guidelines for screening and prevention are limited or not available High-Risk Genes ALK, APC, BMPR1A, BRCA1, BRCA2, CDC73, CDH1, CDKN2A, EPCAM, FH, FLCN, MEN1, MLH1, MSH2, MSH6, MUTYH, NF1, NF2, PALB2, PHOX2B, PMS2, PRKAR1A, PTCH1, PTEN, RB1, RET, SDHB, SDHD, SMAD4, STK11, TP53, TSC1, TSC2, VHL, WT1 Moderate-Risk Genes ATM, BRIP1, CHEK2, RAD51C, RAD51D Newer-Risk Genes AXIN2, BAP1, BARD1, CDK4, DICER1, FANCC, HOXB13, MAX, MET, MITF, NBN, NTHL1, POLD1, POLE, POT1, SCG5/GREM1, RECQL, SDHA, SDHAF2, SDHC, SMARCA4, SMARCB1, SUFU, TMEM127 10

12 Data Analysis and Variant Classification Process Every variant identified at GeneDx goes through a comprehensive review process as described below. 11 AC GT Technical Data Analysis Technical review of raw data Confirmation of identified variants by Sanger sequencing, microarray, MLPA or other appropriate method Determine nomenclature and technical parameters (e.g. coverage, mosaicism, heteroplasmy) Clinical Review In-depth analysis of the variant within clinical context in literature (e.g. segregation, casecontrol studies, co-occurrence with a known pathogenic variant) and patients clinical information Consultation and collaboration with recognized scientific experts Performed by board-certified/eligible genetic counselors REPORT Reporting Results summarized in clear, concise and thoughtfully written reports customized to the patient tested Reports include clinical references, as well as appropriate medical management, patient educational material and other resources, when available Written and signed by genetic counselors and board-certified medical and molecular geneticists We support the community by consistently sharing our data in publically available variant databases and are the largest commercial laboratory contributor to ClinVar. AC GT REPORT Literature and Database Review Comprehensive database and literature review, including Human Gene Mutation Database, ClinVar, as well as gene-specific, population and internal databases Review of output from in-silico protein and splicing prediction models, as well as evolutionary conservation data Analysis of functional impact, including assessing structural/functional domain and predicted effect on protein Performed by PhD-level analysts trained in molecular genetics and/or biochemistry Final Review Detailed review of cumulative evidence and final classification of variants in line with 2015 ACMG guidelines: Pathogenic, Likely Pathogenic, Variant of Uncertain Significance (VUS), Likely Benign and Benign Performed by board-certified medical and molecular geneticists with specific expertise in the disease area and testing platform Variant Follow-Up Complimentary Variant Testing Program available to eligible families to aid in variant classification Re-evaluation of variants incorporates literature and database review, segregation and clinical data, when available Applies to variants identified in a new patient or upon client request, when it has been more than 6 months since the variant was last vetted or pertinent, new data is available Updated results report provided to the ordering healthcare provider for any one-step classification change involving a VUS, Likely Pathogenic Variant or Positive Continued communication with clients to discuss cases and results

13 Patient Name: Date of Birth: Gender: M / F Ethnicity: Phone: Date Completed: Please complete the below questionnaire to assist your healthcare provider in determining if your personal or family history may be placing you or other family members at increased risk to develop cancer, and if you may be eligible for genetic testing (which is often done via a blood test). Tips: Each row should be completed independently Affected relatives on your mother s side of the family should be listed in the pink boxes and affected relatives on your father s side of the family should be listed in the blue boxes Age at diagnosis is the age at which the cancer was diagnosed Other friends and family can assess their cancer risk by going to where they can complete this same form and share it with a healthcare professional. Past genetic testing for cancer: Self Relative Result: Breast and Ovarian Cancer BRCA1 or BRCA2 mutation positive You, siblings, and children: Include yourself, siblings, children, grandchildren, nieces, nephews, great-grandchildren You / Relative Age at diagnosis Maternial Relatives: Include mother and maternal half-siblings, aunts, uncles, grandparents, great-grandparents, great-aunts, great-uncles, first cousins Relative Age at diagnosis Paternal Relatives: Include father and paternal half-siblings, aunts, uncles, grandparents, great-grandparents, great-aunts, great-uncles, first cousins Relative Ashkenazi Jewish ancestry N/A N/A N/A Breast cancer A second, separate diagnosis of breast cancer (second primary) Breast cancer in both breasts (bilateral breast cancer) Triple negative breast cancer* (If you are unsure, please do not add) Male breast cancer Ovarian cancer Pancreatic cancer Prostate cancer * Triple negative breast cancer refers to three receptors: Estrogen Receptor (ER) negative, Progesterone Receptor (PR) negative, HER2neu negative Age at diagnosis First name Last name Caribbean Central/South American Ashkenazi Jewish Hispanic Other: Mailing address City State Zip code Home phone Work phone Patient's primary language if not English Acct # Account Name Physician NPI # Genetic Counselor Street address 1 Street address 2 City State Zip code Phone Fax (important) Beeper Physician or GC/Acct # Fax#/ /CE # Physician or GC/Acct # Fax#/ /CE # Medical record # Specimen ID Date sample obtained (mm/dd/yy) Blood in EDTA (5-6 ml in lavender top tube) DNA (>20 ug): Tissue source concentration (ug/ml) total Volume (ul) Oral Rinse (At least 30 ml of Scope oral rinse in a 50 ml centrifuge tube) Buccal Swab Other (Call lab) Clinical Diagnosis: ICD-10 Codes: Age at Initial Presentation: consented to genetic testing. Medical Professional Signature (required) Date Patient Consent (sign here or on the consent document) I have read the Informed Consent document and I give permission to GeneDx to perform genetic testing as described. I also give permission for my specimen and clinical information to be used in de-identified studies at GeneDx to improve genetic testing and for publication, if appropriate. My name or other personal identifying information will not be used in or linked to the results of any studies and publications. I also give GeneDx permission to inform me or my health care provider in the future about research opportunities, including treatments for the condition in my family. Check this box if you wish to opt out of being contacted for research studies. Patient/Guardian Signature Insurance Bill PATIENT STATUS ONE MUST BE CHECKED Hospital Inpatient Hospital Outpatient Not a Hospital Patient Referral/Prior Authorization # GeneDx Benefit Investigation # Insurance Carrier Policy Name Hold sample for Benefit Investigation (only if OOP cost is >$100) Please attach copy of Referral/authorization Insurance ID # Group # Name of Insured Date of Birth Insurance Address City State Zip Relationship to Insured Child Spouse Self Other Secondary Insurance Insurance ID# Group # Name of Insured Date of Birth Carrier Name Relationship to Insured Child Spouse Self Other Please include a copy of the front and back of the patient s insurance card (include secondary when applicable) If you would like to expedite an assessment of your possible eligibility for GeneDx s financial assistance program (FAP), please provide the number of your household members and the annual income of your household $. GeneDx may require additional information from you to complete an application for GeneDx s financial assistance program. I represent that I am covered by insurance and authorize GeneDx, Inc. to give my designated insurance carrier, health plan, or third party administrator (collectively "Plan") the information on this form and other information provided by my health care provider necessary for reimbursement. I authorize Plan benefits to be payable to GeneDx. I understand that GeneDx will attempt to contact me if my out-of-pocket responsibility will be greater than $100 per test (for any reason, including co-insurance and deductible, or non-covered services). If GeneDx is unsuccessful in its attempts to contact me, I understand that it will be my responsibility to contact GeneDx to determine my out-of-pocket cost and to pay my out-of-pocket responsibility. I will cooperate fully with GeneDx by providing all necessary documents needed for Plan billing and appeals. I understand that I am responsible for sending GeneDx any and all of the money that I receive directly from my Plan in payment for this test. Reasonable collection and/or attorney s fees, including filing and service fees, shall be assessed if the account is sent to collection but said fees shall not exceed those permitted by state law. I permit a copy of this authorization to be used in place of the original. Patient Signature (required) Date I understand that my credit card will be charged the full amount for the testing. GeneDx Account # Please bill my credit card (all major cards accepted) MasterCard Visa Discover American Express Hospital/Lab Name Name as it appears on card Contact Name Account Number Expiration date CVC Address Signature Date City State Zip Code For GeneDx Use Only Phone Fax GeneDx, Inc. 09/ Perry Parkway, Gaithersburg, MD T: (888) (Toll-Free), (301) F: (201) Page 1 of 6 Date Tools for Your Practice SCREEN EDUCATE DIAGNOSE MANAGE Family History Questionnaire for Hereditary Cancer Syndromes OncoGeneDx Test Requisition Form Patient Information Sample Information Patient Questionnaire: HBOC only Hereditary Cancer Genetic Testing Gender Male Female Date of birth (mm/dd/yy) Ancestry Caucasian Eastern European Northern European Western European Native American Middle Eastern African American Asian Pacific Islander Ordering Account Information Reporting Preference*. Care Evolve Fax *If unmarked, we will use the account's default preferences or fax to new clients. Patient has had a blood transfusion Yes No Date of last transfusion / / (2-4 weeks of wait time is required for some testing) Specimens are not accepted for patients who have had allogeneic bone marrow transplants Treatment-Related RUSH: (If known, please provide date) Statement of Medical Necessity This test is medically necessary for the diagnosis or detection of a disease, illness, impairment, symptom, syndrome or disorder. The results will determine my patient's medical management and treatment decisions. The person listed as the Ordering Physician is authorized by law to order the tests(s) requested herein. I confirm that I have provided genetic testing information to the patient and the patient has Send Additional Report Copies To: Check this box if you are a New York state resident, and give permission for GeneDx to retain any remaining sample longer than 60 days after the completion of testing. Payment Options Institutional Bill Patient Bill Amount my GENETICS tree A Comprehensive Guide Identification Materials Testing Patient Support GeneDx provides unique tools to help identify individuals at risk for hereditary cancer, including: A variety of patient educational materials are available through GeneDx, including: GeneDx strives to make the genetic testing process as smooth as possible for patients and providers: After testing, GeneDx offers numerous tools to assist with patient management, including: MyGeneticsTree.com, a web based family history tool that identifies individuals who meet criteria for hereditary cancer testing and can be completed prior to a scheduled visit Family History Forms, a questionnaire which can help determine if individuals or other family members are candidates for genetic testing Patient-friendly guides and panel fact sheets which can be referenced while discussing genetic testing options Patient videos, providing test specific details and information oncology, a website discussing hereditary cancer and testing options Local sales representatives can help coordinate testing Genetic counselors are available to support test selection and education Easy to complete requisition and family history forms Patient Friendly Reports that provide an explanation and discussion of individual test results and management options Lifetime risk assessment materials outlining cancer risks based on the test results Post-test genetic counseling is available upon request 12

14 law. I permit a copy of this authorization to be used in place of the original. Patient Signature (required) Date GeneDx Account # Hospital/Lab Name Contact Name Address City State Zip Code Phone Fax Name as it appears on card Account Number Expiration date CVC Signature Date How to Order Ordering with a Requisition 1. Download the test requisition forms from the GeneDx website: 2. Complete all the forms with the required information 3. Ship completed forms along with appropriate patient sample to the following address: Accessions GeneDx 207 Perry Parkway Gaithersburg, MD OncoGeneDx Test Requisition Form Patient Information Sample Information First name Last name Medical record # Specimen ID Date sample obtained (mm/dd/yy) Gender Male Female Date of birth (mm/dd/yy) Blood in EDTA (5-6 ml in lavender top tube) Ancestry Caucasian Eastern European Northern European Western European Native American Middle Eastern DNA (>20 ug): Tissue source concentration (ug/ml) total Volume (ul) African American Asian Pacific Islander Oral Rinse (At least 30 ml of Scope oral rinse in a 50 ml centrifuge tube) Caribbean Central/South American Buccal Swab Ashkenazi Jewish Hispanic Other: Other (Call lab) Patient has had a blood transfusion Yes No Date of last transfusion / / Mailing address (2-4 weeks of wait time is required for some testing) Specimens are not accepted for patients who have had allogeneic bone marrow transplants City State Zip code Treatment-Related RUSH: (If known, please provide date) Home phone Work phone Clinical Diagnosis: ICD-10 Codes: Age at Initial Presentation: Patient's primary language if not English Statement of Medical Necessity Ordering Account Information This test is medically necessary for the diagnosis or detection of a disease, illness, impairment, symptom, syndrome or disorder. The results will determine my Acct # Account Name patient's medical management and treatment decisions. The person listed as the Reporting Preference*. Care Evolve Fax Ordering Physician is authorized by law to order the tests(s) requested herein. I confirm *If unmarked, we will use the account's default preferences or fax to new clients. that I have provided genetic testing information to the patient and the patient has consented to genetic testing. Physician NPI # Genetic Counselor Medical Professional Signature (required) Date Patient Consent (sign here or on the consent document) Street address 1 I have read the Informed Consent document and I give permission to GeneDx to Street address 2 perform genetic testing as described. I also give permission for my specimen and clinical information to be used in de-identified studies at GeneDx to improve genetic City State Zip code testing and for publication, if appropriate. My name or other personal identifying information will not be used in or linked to the results of any studies and publications. Phone Fax (important) I also give GeneDx permission to inform me or my health care provider in the future about research opportunities, including treatments for the condition in my family. Beeper Check this box if you wish to opt out of being contacted for research studies. Send Additional Report Copies To: Check this box if you are a New York state resident, and give permission for GeneDx to retain any remaining sample longer than 60 days after the completion of testing. Physician or GC/Acct # Fax#/ /CE # Physician or GC/Acct # Fax#/ /CE # Patient/Guardian Signature Date Payment Options Insurance Bill PATIENT STATUS ONE MUST BE CHECKED Hospital Inpatient Hospital Outpatient Not a Hospital Patient Referral/Prior Authorization # GeneDx Benefit Investigation # Insurance Carrier Policy Name Hold sample for Benefit Investigation (only if OOP cost is >$100) Please attach copy of Referral/authorization Insurance ID # Group # Name of Insured Date of Birth Insurance Address City State Zip Relationship to Insured Child Spouse Self Other Secondary Insurance Insurance ID# Group # Name of Insured Date of Birth Carrier Name Relationship to Insured Child Spouse Self Other Please include a copy of the front and back of the patient s insurance card (include secondary when applicable) If you would like to expedite an assessment of your possible eligibility for GeneDx s financial assistance program (FAP), please provide the number of your household members and the annual income of your household $. GeneDx may require additional information from you to complete an application for GeneDx s financial assistance program. I represent that I am covered by insurance and authorize GeneDx, Inc. to give my designated insurance carrier, health plan, or third party administrator (collectively "Plan") the information on this form and other information provided by my health care provider necessary for reimbursement. I authorize Plan benefits to be payable to GeneDx. I understand that GeneDx will attempt to contact me if my out-of-pocket responsibility will be greater than $100 per test (for any reason, including co-insurance and deductible, or non-covered services). If GeneDx is unsuccessful in its attempts to contact me, I understand that it will be my responsibility to contact GeneDx to determine my out-of-pocket cost and to pay my out-of-pocket responsibility. I will cooperate fully with GeneDx by providing all necessary documents needed for Plan billing and appeals. I understand that I am responsible for sending GeneDx any and all of the money that I receive directly from my Plan in payment for this test. Reasonable collection and/or attorney s fees, including filing and service fees, shall be assessed if the account is sent to collection but said fees shall not exceed those permitted by state Institutional Bill Patient Bill Amount I understand that my credit card will be charged the full amount for the testing. Please bill my credit card (all major cards accepted) MasterCard Visa Discover American Express For GeneDx Use Only GeneDx, Inc. 09/ Perry Parkway, Gaithersburg, MD T: (888) (Toll-Free), (301) F: (201) Page 1 of 6 Ordering Through Our Online Portal GeneDx is committed to providing an easy to use online platform to order genetic tests. Our online portal makes the ordering process simple and straightforward. Providers can now upload clinical information electronically, track the progress of an order, and receive results instantaneously through the portal. The portal can be accessed from our website Additionally, GeneDx forms can also be easily accessed for digital or print use at Specimen Requirements Blood in EDTA (5-6 ml in lavender top tube) Oral Rinse in a 50 ml centrifuge tube (at least 30 ml of Scope oral rinse) DNA (>20 ug) Buccal Swab We provide specimen collection kits to health care providers upon request. To place an order for kits, please visit our website: or us at zebras@genedx.com 13

15 Billing Policy Commercial Insurance All commercial insurance is accepted. A benefit investigation is performed. We work with insurance carriers and patients to minimize the out-of-pocket cost to patients. Medicare/Medicaid Medicare is accepted but an Advance Beneficiary Notice is required for patients who do not meet Medicare criteria. Medicaid coverage varies by state; Medicaid will not cover genetic testing in most cases. Institutional A referring institution is billed directly if a GeneDx Institutional Account has been established. A GeneDx Institutional Account allows the referring physician to submit samples through their facility s send-out laboratory. To set up an institutional account, please call us at Self-Pay A payment plan is available for patients who are financially challenged or those who do not have insurance. For more information, please call us at Notes 14

16 About GeneDx GeneDx was founded in 2000 by two scientists from the National Institutes of Health (NIH) to address the needs of patients diagnosed with rare disorders and the clinicians treating these conditions. Today, GeneDx has grown into a global industry leader in genomics, having provided testing to patients and their families in over 55 countries. Led by its world-renowned clinical genomics program, and an unparalleled comprehensive genetic testing menu, GeneDx has a continued expertise in rare and ultra-rare disorders. Additionally, GeneDx also offers a number of other genetic testing services, including: diagnostic testing for hereditary cancers, cardiac, mitochondrial, and neurological disorders, prenatal diagnostics, and targeted variant testing. At GeneDx, our technical services are backed by our unmatched scientific expertise and our superior customer support. Our growing staff includes more than 35 geneticists and 140 genetic counselors specializing in clinical genetics, molecular genetics, metabolic genetics, and cytogenetics who are just a phone call or away to assist you with your questions and testing needs. We invite you to visit our website: to learn more about us. 207 Perry Parkway Gaithersburg, MD T (Toll-free), F E zebras@genedx.com GeneDx, Inc. All rights reserved V2 12/2017 Information current as of 12/2017