A functional assay–based procedure to classify mismatch repair gene variants in Lynch syndrome

PurposeTo enhance classification of variants of uncertain significance (VUS) in the DNA mismatch repair (MMR) genes in the cancer predisposition Lynch syndrome, we developed the cell-free in vitro MMR activity (CIMRA) assay. Here, we calibrate and validate the assay, enabling its integration with in silico and clinical data.MethodsTwo sets of previously classified MLH1 and MSH2 variants were selected from a curated MMR gene database, and their...