Variants of uncertain clinical significance in hereditary breast and ovarian cancer genes: best practices in functional analysis for clinical annotation

Since the identification and cloning of BRCA1 in 1994,1 and shortly thereafter of BRCA2 ,2 genetic tests of germline DNA to identify pathogenic variants in genes linked to hereditary breast and ovarian cancer (HBOC) have become mainstream.3 These tests are critical to identify women at increased risk relative to the general population. Women at moderate risk (2≤relative risk (RR) null 4), including those with BRCA1 and BRCA2 pathogenic variants,...