Among individuals with LS who did not meet Medicare criteria, the majority was found to have P/LP variants in PMS2. This finding is not unexpected given that PMS2 has a considerably lower penetrance for CRC than other LS genes17,18 and is less likely to result in an individual or family-level phenotype meeting LS clinical criteria.1,19 Moreover, PMS2 P/LP variant prevalence has been found to be significantly higher in population-level studies than previous estimates derived from high-risk cohorts.1 This evidence concerns the gene PMS2 and colorectal carcinoma.