ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.962G>A (p.Arg321Gln)

gnomAD frequency: 0.00001  dbSNP: rs2066399994
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002511310 SCV002820556 likely pathogenic not provided 2023-01-10 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; This variant is associated with the following publications: (PMID: 33045145, 27759048, 35761346)
Labcorp Genetics (formerly Invitae), Labcorp RCV005227793 SCV005863056 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2024-12-18 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 214 of the MITF protein (p.Arg214Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Waardenburg syndrome (PMID: 27759048). ClinVar contains an entry for this variant (Variation ID: 1878809). 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%. 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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