ClinVar Miner

Submissions for variant NM_001354604.2(MITF):c.989G>A (p.Arg330His)

gnomAD frequency: 0.00001  dbSNP: rs763119975
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Total submissions: 2
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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 RCV000659863 SCV000781745 uncertain significance Waardenburg syndrome type 2A 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV002530558 SCV003482753 uncertain significance Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 223 of the MITF protein (p.Arg223His). This variant is present in population databases (rs763119975, gnomAD 0.003%). This missense change has been observed in individual(s) with MITF-related conditions (PMID: 30549420). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 547532). 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 expected to disrupt MITF protein function with a positive 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.

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