Probing structure-function relationships in missense variants in the carboxy-terminal region of BRCA1.

Journal Article (Journal Article)

Germline inactivating variants in BRCA1 lead to a significantly increased risk of breast and ovarian cancers in carriers. While the functional effect of many variants can be inferred from the DNA sequence, determining the effect of missense variants present a significant challenge. A series of biochemical and cell biological assays have been successfully used to explore the impact of these variants on the function of BRCA1, which contribute to assessing their likelihood of pathogenicity. It has been determined that variants that co-localize with structural or functional motifs are more likely to disrupt the stability and function of BRCA1. Here we assess the functional impact of 37 variants chosen to probe the functional impact of variants in phosphorylation sites and in the BRCT domains. In addition, we perform a meta-analysis of 170 unique variants tested by the transcription activation assays in the carboxy-terminal domain of BRCA1 using a recently developed computation model to provide assessment for functional impact and their likelihood of pathogenicity.

Full Text

Duke Authors

Cited Authors

  • Carvalho, RS; Abreu, RBV; Velkova, A; Marsillac, S; Rodarte, RS; Suarez-Kurtz, G; Iversen, ES; Monteiro, ANA; Carvalho, MA

Published Date

  • January 2014

Published In

Volume / Issue

  • 9 / 5

Start / End Page

  • e97766 -

PubMed ID

  • 24845084

Pubmed Central ID

  • PMC4028255

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0097766


  • eng