Multimodal assessment of protein functional deficiency supports pathogenicity of BRCA1 p.V1688del.

ABSTRACT: Unequivocal discrimination between neutral variants and deleterious mutations is crucial for appropriate counseling of individuals with a BRCA1 or BRCA2 sequence change. An increasing number of variants of uncertain significance (VUS) are being identified, the unclassified biological effect of which poses clinical concerns. A multifactorial likelihood-based approach recently suggested disease causality for BRCA1 p.V1688del, a VUS recurrent in Italian breast/ovarian cancer families. Whether and how this single amino acid deletion in the BRCA1 COOH terminus (BRCT) domain affects the function of the mutant protein (DeltaValBRCA1) has not been elucidated. We undertook comprehensive functional characterization of DeltaValBRCA1, comprising comparative structural modeling, analysis of protein sta

SUBMITTER: De Nicolo A 

PROVIDER: S-EPMC2748232 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature