ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.653C>T (p.Ala218Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003781005 SCV004569517 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 111 of the MITF protein (p.Ala111Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with clinical features of MITF-related conditions (PMID: 24194866, 31427586). 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 RCV004780643 SCV005389358 uncertain significance not provided 2024-04-30 criteria provided, single submitter clinical testing Observed in individuals with clinical features of Waardenburg syndrome in published literature (PMID: 31427586, 24194866); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20478267, 24194866, 29115496, 33045145, 31427586)

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