MLH1 and cancer: Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer‐predisposition syndrome, caused by biallelic germline pathogenic variants affecting one of the four mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. CMMRD typically manifests in childhood or adolescence as one of a broad range of malignancies, primarily of the hematopoietic system and brain, as well as colorectal and other cancers associated with heterozygous germline MMR pathogenic variants (Lynch syndrome).