Population risk profiling for breast, ovarian and colorectal cancers would be highly clinically valuable: frequency-penetrance profiles of pathogenic variants in BRCA1, BRCA2, MLH1 and MSH2 with breast, ovarian and colorectal cancers, respectively, are strong [13, 14]; breast and colorectal cancers are common and account for a large proportion of cancer deaths in the UK [1, 15]; and effective risk-reducing measures, such as screening, chemoprevention and surgery, are widely available for all three cancers [16, 17]. This evidence concerns the gene MSH2 and colorectal cancer.