While further validation of the pathogenicity of these MMR gene missense variants is needed, the observation from our study that six MMR gene missense variants classified as VUS by ClinVar were identified in individuals who developed MSS CRCs may warrant further consideration by organizations working towards implementing population-based screening programs for Lynch syndrome that are based on screening CRCs via MMR immunohistochemistry for evidence of tumor mismatch repair deficiency before subsequent germline MMR gene testing. This evidence concerns the gene MRC1 and Lynch syndrome.