BRCA1 and ovarian carcinoma: 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.