ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.1516G>C (p.Gly506Arg)

dbSNP: rs531830542
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002251675 SCV002522104 uncertain significance not provided 2022-04-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV003094100 SCV003453398 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 399 of the MITF protein (p.Gly399Arg). This variant is present in population databases (rs531830542, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of Waardenburg Syndrome, type 2A (PMID: 26850479). ClinVar contains an entry for this variant (Variation ID: 1687701). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MITF protein function. 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.
PreventionGenetics, part of Exact Sciences RCV003971211 SCV004778443 uncertain significance MITF-related disorder 2024-02-20 no assertion criteria provided clinical testing The MITF c.1195G>C variant is predicted to result in the amino acid substitution p.Gly399Arg. This variant has been reported in the heterozygous state in a patient with hearing loss and a hypopigmented streak on the skin (Tekin et al. 2016. PubMed ID: 26850479). This variant is reported in 0.040% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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