ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.669G>A (p.Met223Ile)

dbSNP: rs1032758072
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659860 SCV000781741 likely benign Waardenburg syndrome type 2A 2016-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003767913 SCV004580390 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2024-10-23 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 116 of the MITF protein (p.Met116Ile). 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. ClinVar contains an entry for this variant (Variation ID: 547529). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
GeneDx RCV004777814 SCV005391895 uncertain significance not provided 2024-03-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 27640074)
PreventionGenetics, part of Exact Sciences RCV003983159 SCV004800322 uncertain significance MITF-related disorder 2024-02-02 no assertion criteria provided clinical testing The MITF c.348G>A variant is predicted to result in the amino acid substitution p.Met116Ile. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely benign by one submitter in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/547529/). 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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