O08: Assessing the pathogenicity of BRCA1 BRCT domain variants of uncertain significance (VUS)

Between 5-10% of breast and 20-25% of ovarian cancers are inherited. The majority of hereditary cases are caused by pathogenic germline variants in the tumor suppressor genes, BRCA1 and BRCA2. Genetic testing is used to identify pathogenic BRCA heterozygotes who would subsequently benefit from personalized screening, preventative and management plans. However, its widespread implementation has resulted in a significant increase in findings of variants of uncertain significance (VUS) - DNA sequence variants with uncertain effects on disease risk.