ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.1157G>A (p.Arg386Gln)

gnomAD frequency: 0.00004  dbSNP: rs775320252
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV002284452 SCV002010535 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002259067 SCV002536420 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-20 criteria provided, single submitter curation
GeneDx RCV002284452 SCV002574613 uncertain significance not provided 2022-03-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV002549995 SCV003010912 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 279 of the MITF protein (p.Arg279Gln). This variant is present in population databases (rs775320252, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MITF-related conditions. ClinVar contains an entry for this variant (Variation ID: 809506). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MITF protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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