Pathogenic variants (disease-causing) in the MITF gene are associated with an increased lifetime risk of melanoma (skin cancer) and preliminary evidence has been associated with higher risk of kidney cancer; however, exact risk estimates are unknown due to its rarity. Not everyone with a pathogenic variant in the MITF gene will develop cancer. There are some variants, including p.E318K, that predispose people to multiple moles (nevi), and studies report that this variant confers several-fold increased melanoma risk compared with the general population. Management of MITF–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early. MITF variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in MITF exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
