As a proof of principle, we conducted an analysis of a large set of missense variants in the breast and ovarian cancer susceptibility gene BRCA1. Women who inherit inactivating mutations in BRCA1 are at a significantly increased risk of developing early-onset breast and ovarian cancers.4 Classification of BRCA1 variants as pathogenic or not pathogenic have implications for increased surveillance, prophylactic surgery and increasingly to inform therapy. This evidence concerns the gene BRCA1 and ovarian cancer.