It should be noted, that 18 mismatch repair variants of uncertain significance (MLH1, MSH2, MSH6, PMS1, and PMS2 with MAF <1% of general populations) found in 15 early-onset CRC patients could be very relevant, in particular if the tumors have high-level microsatellite instability (MSI-H) (14). This evidence concerns the gene MSH2 and colorectal carcinoma.