Clinical Variant Classification: A Comparison of Public Databases and a Commercial Testing Laboratory

Abstract

With the increasing use of clinical genetic testing for hereditary cancer risk, accurate variant classification is vital to ensuring appropriate medical management. There is a growing move to consult public databases following receipt of a genetic test result from a clinical laboratory; however, we show that up to 26.7% of variants in <i>BRCA1</i> and <i>BRCA2</i> have discordant classifications between ClinVar and a reference laboratory. The findings presented in this paper serve as a note of caution regarding the utility of database consultation.