1 Individuals with LS generally have increased risk of developing early-onset colorectal cancer (CRC) and some extracolonic cancers, such as endometrial cancer (EC). Understanding the cancer risk associated with likely pathogenic or pathogenic variants affecting MMR gene function (jointly referred to as path_MMR) is important for informing management plans for prevention and early detection of LS-associated cancers. The gene discussed is MRC1; the disease is Leigh syndrome.