Here, we describe the design and validation of BRCAplus, a comprehensive custom clinical diagnostic assay that detects mutations in the six high-risk breast cancer susceptibility genes: BRCA1, BRCA2, CDH1, PTEN, TP53 and STK11 (Table 1) using NGS and array comparative genomic hybridization (aCGH). The gene discussed is BRCA1; the disease is breast cancer.