Myriad study shows discrepancies in Clinvar database for hereditary cancer classification

April 18, 2017 – 8:06 AM | By Andrea Gonzalez | No comments yet

By Omar Ford, Staff Writer

Public genetic databases could have a discrepancy in identifying BRCA1 and BRCA2 variant classifications, which can introduce uncertainty and diminish patient care, according to a study by Myriad Genetics Inc. and researchers from Gradishar from the Feinberg School of Medicine at Northwestern University. The study was published in this month’s edition of the journal The Oncologist and results from it show that the Clinvar public database provided discrepant variant classifications more than 26 percent of the time. The Salt Lake City-based company’s study evaluated 4,250 BRCA1 and BRCA2 variants.

Clinvar is a freely accessible public archive of reports of the relationships among human variations and phenotypes hosted by the National Center for Biotechnology Information (NCBI) and supported by intramural National Institutes of Health (NIH) funding.

“These research databases are not appropriate for use in any kind of clinical decision making by any labs at all,” Johnathan Lancaster, Myriad chief medical officer, told Medical Device Daily. “Using Clinvar and public databases to generate clinical test results is the equivalent of using Wikipedia. Some of it’s right and some of it’s wrong, but without being a subject matter expert you don’t know which is which.”

Overall, 73.2 percent of variant classifications analyzed were fully concordant, while 26.7 percent were not. Most of the discordant classifications had definitive classifications of pathogenic or benign from Myriad, compared to “variant of uncertain significance” (VUS) classifications in the public database.

As a repository of actual patient results, data from the study shows that different labs are providing different results to patients for the same genetic mutation. The company said that by definition, this means that some patients are receiving incorrect results that may have life-changing or -threatening implications.

These findings are consistent with previously published studies. A study by Vail et al. compared the interpretation of more than 2,000 BRCA1/2 variants among five public databases and found substantial disparity of variant classifications among and within publicly accessible variant databases. VUSs in particular, there is no agreement once the variant is observed in a least four of the five databases in this study. Another study by Balmana et al. assessed conflicting interpretations of genetic variants in the Prospective Registry of Multiplex Testing (PROMPT) and found significant conflicting interpretations of genetic variants in that database. Specifically, among variants entered into the PROMPT registry database with classifications from multiple labs, 26 percent had discrepant classifications; 36 percent of which would affect patient management.

Myriad has developed the Myrisk Hereditary cancer test, a 28-gene panel that identifies an elevated risk for eight important cancers.

“Myriad’s hereditary cancer testing portfolio relies on a scientifically validated robust process for variant classification, that’s not mirrored in anyway by competitors and key findings confirm that,” Lancaster said. “The bottom line is, if you don’t invest in the science and the process to enable excellence for your hereditary cancer genetic testing, you’re not going to get excellence in your hereditary cancer genetic testing.


Myriad isn’t resting on its laurels when it comes to its hereditary cancer offerings. The company has just recently had a resurgence in its hereditary cancer offerings. The company’s hereditary cancer test segment came in about $2.5 million above consensus, bringing in $144 million. Myriad executives noted the segment benefited from both a “seasonally stronger” quarter as well as “robust volume growth” in the oncology segment.

“Core hereditary cancer revenues grew 3 percent quarter over quarter, reversing a negative trend of the past year, helped by stability in the oncology market, which rose sequentially for the first time in 18 months,” said Brandon Couillard, an analyst with Jefferies and Co.

More competition in hereditary cancer testing is emerging. In May, Madison, N.J.-based Quest Diagnostics Inc. launched two new panels for hereditary breast cancer testing: the Myvantage Hereditary Comprehensive Cancer Panel and the Qvantage Hereditary Women’s Health Cancer Test.

Myriad is also stretching beyond hereditary cancer tests. In 2Q17, non-HC tests accounted for 67 percent of volumes, but only 27 percent of revenues.

In August 2016, the company entered the neuroscience market with its acquisition of Assurex Health for about $225 million up front and possibly $185 million in additional performance-based payments. (See Medical Device Daily, Aug. 4, 2016.)

Assurex Health is an informatics-based precision medicine company that provides treatment decision support to health care providers for mental health patients.



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