Interestingly, in family F-4 (Figure 3b), the index case (P-03) carrier of the MLH1 c.1558+1G>A pathogenic variant was affected by CRC, with clonal MLH1 hypermethylation in those areas of tumors showing IHC clonal loss of MLH1 expression. This evidence concerns the gene MLH1 and colorectal carcinoma.