ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.639C>G (p.Asn213Lys)

dbSNP: rs137944487
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825372 SCV000966667 uncertain significance not specified 2019-02-06 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Asn106Lys variant in MITF has not been previously reported in individuals with hearing loss or Waardenburg syndrome, but has been identified in 0.003% (5/128938) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of this variant is uncertain, these data suggest that it is more likely to be benign. ACMG/AMP criteria: BP4.
GeneDx RCV001776044 SCV002013332 uncertain significance not provided 2023-03-15 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; This variant is associated with the following publications: (PMID: 27349893)
Labcorp Genetics (formerly Invitae), Labcorp RCV001858387 SCV002259163 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 106 of the MITF protein (p.Asn106Lys). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 666859). 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.

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