Computational prediction tools and conservation analyses are inconclusive regarding the ….This missense variant replaces glutamic acid with lysine at codon 318 of the MITF protein. Features: Compliance support (CLIA and CAP) Long Term Support Prioritized bug fixes and feature development In addition, this variant has been observed in individuals with a personal and/or family history of renal cell carcinoma (Bertolotto 2011, Ghiorzo 2013, Potrony 2016). 2020Apr01: Clinvar annotation (version 20200316) is available in ANNOVAR now. 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Figure 1. Experimental studies have shown that this variant decreases the SUMOylation of MITF, resulting in altered transcription of target genes and increased colony forming potential (PMID: 22012259, 22080950). This variant is a well-established risk factor for melanoma and renal cell carcinoma (OR 2.95-8.37, depending on family history) (Bertolotto, 2011; Ghiorzo, 2013; Wadt, 2015; Potrony, 2016).
Similarly, the carriers of this variant were reported to have a 5 fold increased risk of developing melanoma, renal cell carcinoma or both these cancers (OR = 5.55 (95% CI 2.59-12.91, Bertolotto_2011). The dataset reflects the state of the ClinVar data as of 2/15/2015 10:18AM PST. The ClinVar database was used to annotate variants of clinical significance. The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine.
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