ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.1130G>A (p.Arg377Gln)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002474172 SCV002770268 uncertain significance not provided 2022-12-21 criteria provided, single submitter clinical testing 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
PreventionGenetics, part of Exact Sciences RCV003408289 SCV004109372 uncertain significance MITF-related disorder 2022-09-13 criteria provided, single submitter clinical testing The MITF c.809G>A variant is predicted to result in the amino acid substitution p.Arg270Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-70008522-G-A), and it has not been reported in the ClinVar database. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV003775534 SCV004578004 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2023-07-19 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 1806743). This variant has not been reported in the literature in individuals affected with MITF-related conditions. This variant is present in population databases (rs542163629, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 270 of the MITF protein (p.Arg270Gln).

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