MSH2 and colorectal carcinoma: Around 1 in 280 of the general population is heterozygous for a pathogenic variant in an MMR gene, MLH1, MSH2 (including deletions of EPCAM), MSH6 or PMS2 (path_MMR), the vast majority of whom are undiagnosed.5–8 Path_MMR heterozygotes have an averaged risk to age 70 years of EC, CRC and ovarian cancer (OC) of 35%, 46% and 11%, respectively,9 although these vary by gene with lower risks of PMS2.