biostudies-literatureUnknown117(7)Gayarre J<h4>Background</h4>Despite a high prevalence of deleterious missense variants, most studies of RAD51C ovarian cancer susceptibility gene only provide in silico pathogenicity predictions of missense changes. We identified a novel deleterious RAD51C missense variant (p.Arg312Trp) in a high-risk family, and propose a criteria to prioritise RAD51C missense changes qualifying for functional analysis.<h4>Methods</h4>To evaluate pathogenicity of p.Arg312Trp variant we used sequence homology, loss of heterozygosity (LOH) and segregation analysis, and a comprehensive functional characterisation. To define a functional-analysis prioritisation criteria, we used outputs for the known functionally confirmed deleterious and benign RAD51C missense changes from nine pathogenicity prediction algorithms.<h4British journal of cancer1048-1062https://www.ebi.ac.uk/biostudies/studies/S-EPMC5625680biostudies-literatureCharacterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.PMC5625680Osorio AGayarre JGarcia MJUrioste MPalacios JBenitez JMartin-Gimeno PPaumard BFernandez VRojo ABarroso Ade la Hoya MCaldes TfalseCharacterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.<h4>Background</h4>Despite a high prevalence of deleterious missense variants, most studies of RAD51C ovarian cancer susceptibility gene only provide in silico pathogenicity predictions of missense changes. We identified a novel deleterious RAD51C missense variant (p.Arg312Trp) in a high-risk family, and propose a criteria to prioritise RAD51C missense changes qualifying for functional analysis.<h4>Methods</h4>To evaluate pathogenicity of p.Arg312Trp variant we used sequence homology, loss of heterozygosity (LOH) and segregation analysis, and a comprehensive functional characterisation. To define a functional-analysis prioritisation criteria, we used outputs for the known functionally confirmed deleterious and benign RAD51C missense changes from nine pathogenicity prediction algorithms.<h42017-01-01T00:00:00Z2017 Sep2026-04-29T08:46:45.001Z2019-03-26T23:57:03ZS-EPMC56256802882976210.1038/bjc.2017.286