MLH1 exon 10 was selected as model system for 3 main reasons: (i) MLH1 is the major gene implicated in Lynch syndrome, one of the most frequent forms of hereditary cancer worldwide, formerly known as hereditary nonpolyposis colorectal cancer (HNPCC), (ii) this gene exhibits a large mutational spectrum, with at least 30% of variants being currently classified as variants of unknown significance and for which large national and international efforts persist in bringing clarification [22,23], and (iii) alterations of potential ESRs were already reported for 3 SNVs in this exon [13,24]. This evidence concerns the gene MLH1 and hereditary cancer.