23andMe, Inc. recently began reporting three pathogenic variants known to increase a person’s risk for breast and ovarian cancer, among other hereditary cancers. These variants, reported by 23andMe as BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, are some of the best studied and published pathogenic variants in Hereditary Breast and Ovarian Cancer syndrome. For many carriers of BRCA1 or BRCA2 pathogenic variants, receiving rapid and appropriate clinical intervention is lifesaving. The Center for Genomic Interpretation calls upon medical insurers to cover confirmatory testing of the BRCA1 185delAG, BRCA1 5382insC, or BRCA2 6174delT variants for 23andMe customers who test positive for any of these three variants.
Customers, patients, clinicians, and policy makers should remain aware that most persons who are, or could be, diagnosed with Hereditary Breast and Ovarian Cancer syndrome through a genetic test will carry pathogenic variants that are not reported in the 23andMe test. Current standards of care and professional clinical judgement should continue to guide the diagnostic testing and care of all patients.
23andMe’s reporting of the BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT variants is FDA authorized. Accuracy studies, as determined by comparison with DNA sequencing and submitted by 23andMe to the FDA, achieved both 100% positive and 100% negative agreement. The study size yielded a false positive rate less than 15% and a false negative rate less than 16% with 95% confidence. The FDA requires confirmatory testing for a positive test result from 23andMe for any of these three variants and genetic counseling before medical treatment options are pursued by a medical professional. The Center for Genomic Interpretation encourages clinicians and patients to select a high-quality diagnostic test for this confirmation, as not all diagnostic laboratories or genetic tests are of equal quality.
It is possible that the breast and ovarian cancer risk estimates of the BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT variants will be modified over time as testing is increasingly available to the general population. The Center for Genomic Interpretation encourages 23andMe and other companies to contribute meaningfully to the public shared knowledge of the cancer risks associated with these and other variants.
About the Center for Genomic Interpretation
The Center for Genomic Interpretation is an independent 501(c)(3) nonprofit driving quality in clinical genetics. The Center works with multiple stakeholders to ensure that genetics patients and consumers receive the most accurate results possible from their clinical genetic testing.
Conflict of Interest Statement
Some of the founders and executives of the nonprofit Center for Genomic Interpretation are former employees of 23andMe, Inc. and other diagnostic companies, including Myriad Genetic Laboratories, Inc. However, the founders and executives do not currently hold financial interests in any diagnostic or direct-to-consumer laboratories or companies.
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