ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1984T>C (p.Ser662Pro)

gnomAD frequency: 0.00012  dbSNP: rs376341411
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Total submissions: 5
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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 RCV000152684 SCV000202056 uncertain significance not specified 2013-07-28 criteria provided, single submitter clinical testing The Ser662Pro variant in WFS1 has not been reported in individuals with hearing loss, but has been identified in 0.05% (2/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Compu tational analyses (biochemical amino acid properties, conservation, AlignGVGD, P olyPhen2, and SIFT) suggest that the Ser662Pro variant may impact the protein, t hough this information is not predictive enough to determine pathogenicity. In s ummary, additional data is needed to determine the clinical significance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850080 SCV002271510 uncertain significance not provided 2022-10-12 criteria provided, single submitter clinical testing 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 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. ClinVar contains an entry for this variant (Variation ID: 166600). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs376341411, gnomAD 0.04%). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 662 of the WFS1 protein (p.Ser662Pro).
Fulgent Genetics, Fulgent Genetics RCV002478442 SCV002792242 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-03-03 criteria provided, single submitter clinical testing
Baylor Genetics RCV003147358 SCV003836305 uncertain significance Wolfram syndrome 1 2022-02-25 criteria provided, single submitter clinical testing
GeneDx RCV001850080 SCV005685757 uncertain significance not provided 2024-07-25 criteria provided, single submitter clinical testing 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; This variant is associated with the following publications: (PMID: 26435059)

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