Indeed, in line with a lower CRC incidence, it has been shown that oncogenic driver mutations in the majority of CRCs from pathogenic PMS2 variant carriers are not related to mutational signatures of MMR deficiency [65], which is in contrast to driver mutations in the majority of LS colorectal tumours associated with other MMR genes [66,67]. Here, PMS2 is linked to mismatch repair cancer syndrome 1.