Functional analysis of <i>MSH2</i> unclassified variants found in suspected Lynch syndrome patients reveals pathogenicity due to attenuated mismatch repair

Abstract

Based on the results from our functional assays, we conclude that the MSH2-M813V variant is not disease causing. The MSH2-Y165D and MSH2-Q690E variants affect MMR function and are therefore likely the underlying cause of familial cancer predisposition. Since the MMR defect is partial, these variants may represent low penetrance alleles.