In the cohort with familial CRC we identified three high-risk pathogenic variants in APC, MSH2 and POLE. The MSH2 variant, c.2168C>T, p.(Ser723Phe) had previously been identified, but since new knowledge have emerged, the variant was reclassified to a likely pathogenic variant from a VUS. This evidence concerns the gene POLE and colorectal carcinoma.