MLH1 and cancer: Germline variants found in cancer patients not only have confirmed the clinical utility of pathogenic mutations in high-penetrant “first wave” (including BRCA1, BRCA2, MLH1, and MSH2) and “second wave” (PALB2, RAD51C, and RAD51D) genes predisposing to common cancers but also have identified dozens of variants with unknown clinical significance (VUS) and variants of the “second wave” moderate penetrance genes (including ATM or CHEK2) [7,11].