Two cases exemplify the utility of splicing profile by capture RNA-seq in identifying PVs in the HBOC predisposition gene BRCA1. In the first case, the proband is a female with Caucasian/Asian descent diagnosed with breast cancer at the age of 25 and 33 years, and high-grade papillary serous ovarian cancer at the age of 44 years. Here, BRCA1 is linked to breast cancer.