ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2407G>A (p.Val803Met)

gnomAD frequency: 0.00001  dbSNP: rs745988826
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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 RCV000220960 SCV000272919 uncertain significance not specified 2016-01-21 criteria provided, single submitter clinical testing The p.Val803Met variant in WFS1 has not been previously reported in individuals with hearing loss or Wolfram syndrome. This variant has been identified in 2/639 96 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs745988826); however, this frequency is not high enoug h to rule out a pathogenic role. Computational prediction tools and conservatio n analyses suggest that the p.Val803Met variant may impact the protein, though t his information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Val803Met variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001857755 SCV002188509 uncertain significance not provided 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 803 of the WFS1 protein (p.Val803Met). This variant is present in population databases (rs745988826, gnomAD 0.003%). This missense change has been observed in individual(s) with optic neuropathy and/or Wolfram‚Äëlike syndrome (PMID: 32700054, 33841295). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 229643). 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 WFS1 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002485410 SCV002788140 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-04-19 criteria provided, single submitter clinical testing

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