ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.1285G>C (p.Glu429Gln)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003149460 SCV003837322 uncertain significance not provided 2023-09-06 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 RCV003778897 SCV004584158 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 glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 322 of the MITF protein (p.Glu322Gln). This variant is present in population databases (rs756384799, gnomAD 0.007%). 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: 2442688). 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 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.
Ambry Genetics RCV005363079 SCV006025764 uncertain significance Hereditary cancer-predisposing syndrome 2025-01-03 criteria provided, single submitter clinical testing The p.E322Q variant (also known as c.964G>C), located in coding exon 9 of the MITF gene, results from a G to C substitution at nucleotide position 964. The glutamic acid at codon 322 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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