Assessment of small in-frame indels and C-terminal nonsense variants of BRCA1 using a validated functional assay.

ABSTRACT: BRCA1 (Breast Cancer 1, early onset) is linked to breast and ovarian cancer predisposition. Still, the risks conferred by a significant portion of BRCA1 variants identified in the population remains unknown. Most of these variants of uncertain significance are missense alterations. However, the functional implications of small in-frame deletions and/or insertions (indels) are also difficult to predict. Our group has previously evaluated the functional impact of 347 missense variants using an extensively validated transcriptional activity assay. Here we show a systematic assessment of 30 naturally occurring in-frame indels located at the C-terminal region of BRCA1. We identified positions sensitive and tolerant to alterations, expanding the knowledge of structural determinants of BRCA1 func

SUBMITTER: Nepomuceno TC 

PROVIDER: S-EPMC9519549 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature