Familial melanoma

Gene: MITF

I don't know

Comment on list classification: There is emerging evidence for significant enrichment of germline p.Glu318Lys variant from MITF gene in melanoma patients in comparison to population control. However, there are no other variants from this gene has been associated with risk of melanoma. This gene has been rated amber with current evidence.

Created: 19 Jun 2026, 4:12 p.m. | Last Modified: 19 Jun 2026, 4:12 p.m.

Panel Version: 2.14

PMID:22012259 (2011) reported the presence of higher than five-fold increased risk of developing melanoma, renal cell carcinoma or both cancers in individuals with germline missense substitution in MITF gene (p.Glu318Lys), when compared with controls.

PMID: 22080950 (2011) reported the whole-genome sequencing of probands from several melanoma families, of which one individual was identified with p.Glu318Lys variant in MITF gene. The MITF variant allele was found in 3/7 melanoma cases assessed in this family, consistent with it being a medium-penetrance melanoma risk variant. This variant was significantly associated with melanoma in a large Australian case-control sample and in an independent case-control sample from the UK. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets.

PMID:42177185 (2026) reported a study of 346 mucosal melanoma patients, of which germline pathogenic variant in MITF (p.Glu318Lys) was identified in six patients, which was a significant enrichment compared to population control rates.

This gene has been associated with relevant susceptibility phenotype in OMIM (MIM #614456) and OMIM record was last accessed 19 June 2026. This gene is included in Cancer panel with 'limited' rating in Gene2Phenotype.

Created: 19 Jun 2026, 3:44 p.m. | Last Modified: 19 Jun 2026, 4:03 p.m.

Panel Version: 2.10

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Melanoma, cutaneous malignant, susceptibility to, 8}, OMIM:614456; melanoma, cutaneous malignant, susceptibility to, 8, MONDO:0013759

Publications

• 22012259
• 22080950
• 42177185

I don't know

The MITF E318K variant was enriched in this retrospective cohort of mucosal melanoma patients compared to population controls (OR 6.0; 95% CI 2.2–13.2).
Sources: Literature

Created: 28 May 2026, 4:33 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mucosal melanoma

Publications

• PMID: 42177185