POLE and familial melanoma: While there are a handful of well-established, rare, high penetrance mutations, such as deleterious variants of CDKN2A, CDK4, BAP1, TERT, POT1, TERF2IP, ACD, POLE, EBF3, GOLM1, and NEK11 associated with familial melanoma, these mutations account for only 30% of familial melanoma cases (44).