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By: Kara Hapke
Following the Supreme Court case decisions of Mayo Collaborative Services v Prometheus Laboratories (2012) and Association for Molecular Pathology v. Myriad Genetics (2013), an increase in the number of genetic testing companies offering BRCA1, BRCA2, PALB2, MUTYH, and RAD51C testing, either individually or as part of a cancer panel, will be observed.
Following the Supreme Court case decisions of Mayo Collaborative Services v Prometheus Laboratories (2012) and Association for Molecular Pathology v. Myriad Genetics (2013), the purpose of this case study is to determine (if applicable) a potential “increase”, “decrease”, or “no change” in the:
NCBI ClinVar contribution data was utilized to identify laboratories conducting genetic testing for BRCA1, BRCA2, PALB2, MUTYH, and RAD51C genetic variations (see: Tables 2-6). Laboratories not contributing to ClinVar were excluded for potential interview, with the exception of Myriad Genetics. Based on the numerical quantity of their ClinVar contribution(s), genetic testing laboratories were classified into three categories: significant contributor, moderate contributor, and minor contributor (see: Table 1). The laboratories were classified into the aforementioned three groups to ensure a thorough and evenly distributed evaluation for anticipated interview selection.
Table 1: Genetic Testing Laboratory Classification based on ClinVar Submission(s)
>1000 Variants AND >250 are Pathogenic
>500 Variants AND >125 are Pathogenic
>100 Variants AND >10 are Pathogenic*
*Minimum ClinVar Contribution for Interview Invitation: >100 Variants AND >10 are pathogenic
Table 2: ClinVar Submitters for BRCA1 Variants
Breast Cancer Information Core (BIC)
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Dept. of Pathology and Laboratory Medicine, Sinai Health System
Michigan Medical Genetics Laboratories, Univ of Michigan
Dept. of Medical Genetics, Oslo Univ. Hosp.
ARUP Laboratories, Molecular Genetics and Genomics
Diagnostic Laboratory, Dept. of Genetics, University Medical Center Groningen
Table 3: ClinVar Submitters for BRCA2 Variants
Research Molecular Genetics Laboratory, Women's College Hopsital, University of Toronto
ARUP Laboratories, Molecular Genetics
DNA and Cytogenetics Diagnostics Unit, Erasmus Medical Center
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
CHEO Genetics Diagnostics Laboratory, Children's Hospital of Eastern Ontario
Genome Diagnostics Laboratory, University Medical Center Utrecht
Lab for Molecular Medicine, Partners HealthCare Personalized Medicine
Foulkes Center Genetics LDI, Lady Davis Institute for Medical Research
Table 4: ClinVar Submitters for PALB2 Variants
Table 5: ClinVar Submitters for MUTYH Variants
Table 6: ClinVar Submitters for RAD51C Variants
Hereditary cancer-predisposing syndrome*
Fanconi anemia, complementation group O*
Table 7: ClinVar Submitters (within the U.S.) Selected for Interview Invitation & Associated Genetic Testing Offerings
Table 8: ClinVar Submitters (within the U.S.) Interviewed
DC-I (Diagnostic Company I)*
DC-II (Diagnostic Company II)*
*Interviewee/Organization Name Redacted for Privacy
Table 8: Genetic Testing Experts Interviewed
GTE-I (Genetic Testing Expert I)*
GTE-II (Genetic Testing Expert II)*
Table 9: Qualitative Interview Questions
Do you offer BRCA1, BRCA2, PALB2, MUTYH, and/or RAD51C testing?
When did you start offering cancer multi-gene panel testing?
Did you exclude BRCA1/2 from cancer gene panels before the Supreme Court decision in Myriad in June 2013?
Did the 2012 Supreme Court decision in Mayo v Prometheus change your genetic testing practices?
Did the patent situation affect data availability, in your view?
What role do use of databases that are freely available (e.g., ClinVar, gnomAD and LOVD) play in clinical interpretation of the results from genetic tests for inherited cancer risk?
What is your opinion on sharing data from the results of your tests with public databases like ClinVar, gnomAD, and LOVD?
How do you arrive at your interpretation of a variant?
What do you think might happen if either individual variants, or associations between variants and diseases/conditions, were to become patent-eligible again?
Is there anyone else whom you believe we should interview?
TBD. Case study currently in progress. See “Note” below.
Due to the overwhelming effects SARS-CoV-2 has had on diagnostic testing laboratories, this qualitative case study has been temporarily halted as of March ‘20. As a result, the present sample size of qualitative interviews with both genetic testing laboratories and genetic testing experts is very small, respectively, is n=2 and n=2. The qualitative interviews will resume once the impact of SARS-CoV-2 has lessened, which is expected to be in Fall ’20.