ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1556C>T (p.Ala519Val)

gnomAD frequency: 0.00001  dbSNP: rs201557396
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Total submissions: 4
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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 RCV000152679 SCV000202045 uncertain significance not specified 2014-09-29 criteria provided, single submitter clinical testing The p.Ala519Val variant in WFS1 has not been previously reported in individuals with hearing loss but has been identified in 0.833% (1/120) of Columbian chromos omes by the 1000 Genomes Project (dbSNP rs201557396). Computational prediction t ools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the Ala519Val variant is uncertain.
GeneDx RCV000767005 SCV000252529 uncertain significance not provided 2021-09-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000767005 SCV002230197 uncertain significance not provided 2022-11-22 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 166592). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs201557396, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 519 of the WFS1 protein (p.Ala519Val).
Fulgent Genetics, Fulgent Genetics RCV002483323 SCV002789678 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-11-20 criteria provided, single submitter clinical testing

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