ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2414G>A (p.Arg805Gln)

gnomAD frequency: 0.00006  dbSNP: rs140667597
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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 RCV000152699 SCV000202076 uncertain significance not specified 2014-08-07 criteria provided, single submitter clinical testing The Arg805Gln variant in WFS1 has not been previously reported in individuals wi th hearing loss, but has been identified in (1/8600) of European American chromo somes and (1/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs140667597). Computational p rediction tools and conservation analyses suggest that the Arg805Gln variant may not impact the protein, though this information is not predictive enough to rul e out pathogenicity. In summary, the clinical significance of the Arg805Gln vari ant is uncertain.
Fulgent Genetics, Fulgent Genetics RCV002492568 SCV002775253 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-02-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002516067 SCV003505075 uncertain significance not provided 2023-06-30 criteria provided, single submitter clinical testing This variant is present in population databases (rs140667597, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 805 of the WFS1 protein (p.Arg805Gln). 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. 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. ClinVar contains an entry for this variant (Variation ID: 166610). This variant has not been reported in the literature in individuals affected with WFS1-related conditions.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV003148662 SCV003804412 uncertain risk allele Wolfram syndrome 1 criteria provided, single submitter research Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs140667597 in Wolfram's syndrome yet.

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