POLE and colorectal carcinoma: As reported by previous studies, the POLE p.Leu424Val mutation frequency in multiple colorectal adenomas or familial CRC cohorts seems to be typically ≤ 0.3% [5, 11, 12, 14, 15], whereas the POLD1 p.Ser478Asn mutation seems to be even less frequent (< 0.1%) [5, 14].