Technical advances in recent years in high throughput DNA sequencing have finally provided enough data to begin testing the accuracy of previously accepted genetic variant interpretation methods. Clinical genetic researchers are starting to realize that genetic variant interpretation has unknowingly been plagued with inadequate methods and biases which have been canonized in the scientific research literature. The research literature suffers from underpowered and inadequately controlled studies with significant bias. These contribute to the greater than 50% false positive rate in variant classifications averaged across the industry.
Few laboratories have the resources or know-how to develop or apply advanced scientific and statistical methodology for the specific genes they test. Most laboratories rely on the minimal standards and guidelines recommended by the American College of Medical Genetics and Genomics. While these 2015 guidelines were successful in raising the quality bar for many laboratories, the intent of these guidelines was to provide a starting point, rather than an endpoint for quality. The ACMG guidelines called on the clinical genetics community to continue to advance by using more stringent and quantitative methods. ClinGen working groups and other consortia across the globe continue to develop and test more advanced methods and would benefit by securely accessing data sets that would allow them to validate methods clinically. CGI is committed to working with for-profit companies by providing appropriate variant classifications and reclassifications with the strictest standard of scientific and statistical evidence. The secure datasets CGI builds with its commercial partners will provide the statistical power necessary for CGI scientists, and consortia collaborators, to make advances in variant classification and reclassification. This will allow CGI’s partner laboratories and companies to provide best-in class variant interpretations. Better clinical science saves more lives.