Tumour characteristics provide evidence for germline mismatch repair missense variant pathogenicity

Background Pathogenic variants in mismatch repair (MMR) genes ( MLH1, MSH2 , MSH6 and PMS2 ) increase risk for Lynch syndrome and related cancers. We quantified tumour characteristics to assess variant pathogenicity for germline MMR genes. Methods Among 4740 patients with cancer with microsatellite instability (MSI) and immunohistochemical (IHC) results, we tested MMR pathogenic variant association with MSI/IHC status, and estimated likelihood...