ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.967A>G (p.Arg323Gly)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Rare Diseases, West China Hospital, Sichuan University RCV005053185 SCV005686820 likely pathogenic Waardenburg syndrome type 2A 2025-01-09 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV005223191 SCV005862384 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2024-10-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 216 of the MITF protein (p.Arg216Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MITF-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MITF protein function with a positive predictive value of 80%. This variant disrupts the p.Arg216 amino acid residue in MITF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20127975, 23787126). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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