Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic.

ABSTRACT: Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts an

SUBMITTER: Ahlborn LB 

PROVIDER: S-EPMC4368840 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature