Integrating Functional and Structural Analyses Improves the Assessment of BRCA1 Missense Variants of Unknown Significance
The correct classification of BRCA1 missense variants presents a challenge to provide accurate genetic counseling and targeted cancer therapy.
To improve the classification of these alterations, we propose an integrated approach: clinical data, protein structure, in silico analyses, and population allele frequency followed by HDR assay and quantitative infrared western blot analyses.
This approach may also be used to assess additional missense VUS in other Hereditary Breast and Ovarian Cancer genes involved in the HDR pathway.
Authors: Charles Yi; Marcy Richardson; Tina Pesaran; Vickie Hsuan; Adam Chamberlin; Lucia Guidugli; J. Parvin; Brigette Tippin Davis; Rachid Karam