MRC1 and polyp of large intestine: In conclusion, in this study, we identified PV/LPV or VUS with prediction of probable damaging effect in genes involved in the DNA-ICLR pathway that may contribute to increase serrated colorectal polyps or carcinoma risk in a subgroup of familial SPS, namely, those with a preferential location of lesions in the proximal/whole-colon and that present a specific somatic signature characterized by defective MGMT and MMR genes.