This is particularly relevant for the PMS2 gene since, based on data from first degree relatives in the Colon Cancer Family Registry, the frequency of PMS2 PV carriers in the general population is 1 in 714 and they may not present as LS due to the low penetrance of PMS2 PV in the heterozygous state [21]. Here, PMS2 is linked to malignant colon neoplasm.