MLH1 and neoplasm: Although there was a low rate of path_MMR in patients with tumours with MLH1 loss on IHC and promoter methylation as a prescreen, we have previously demonstrated that 4/71 (5.6%) individuals with CRC and germline pathogenic variants in MLH1 had evidence of promoter methylation.27 Three of these four fulfilled Amsterdam criteria did not have an IHC prescreen (they were tested after path_MMR was found); therefore, overall MLH1 promotor methylation still left a >10% chance of a germline path_MMR.