Prompted by the fact that mutations occurring in the BRCA1 and BRCA2 genes account for 5–10% of hereditary breast cancer cases [38] and as much as 80% of the variants identified in these genes remain VUS [39], we further evaluated the performance of the prediction algorithms using two benchmarking datasets composed of BRCA1 and BRCA2 variants. Here, BRCA1 is linked to breast cancer.