BRCA1 frameshift variants leading to extended incorrect protein C termini.

ABSTRACT: Carriers of BRCA1 germline pathogenic variants are at substantially higher risk of developing breast and ovarian cancer than the general population. Accurate identification of at-risk individuals is crucial for risk stratification and the implementation of targeted preventive and therapeutic interventions. Despite significant progress in variant classification efforts, a sizable portion of reported BRCA1 variants remain as variants of uncertain clinical significance (VUSs). Variants leading to premature protein termination and loss of essential functional domains are typically classified as pathogenic. However, the impact of frameshift variants that result in an extended incorrect terminus is not clear. Using validated functional assays, we conducted a systematic functional assessment of 1

SUBMITTER: Nepomuceno TC 

PROVIDER: S-EPMC10558845 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature