MSH6 and Lynch syndrome: Therefore, most single variants associated with complex disease are not clinically useful, but some complex diseases are caused by a single pathogenic variants in some genes, including BRCA1 and BRCA2 in hereditary breast cancer and ovarian cancer syndrome [52], MLH1, MSH2, MSH6, and PMS2 in Lynch syndrome [53], and LDLR and PCSK9 in atherosclerotic cardiovascular disease [54].