ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2108G>A (p.Arg703His)

gnomAD frequency: 0.00001  dbSNP: rs1323852277
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001723374 SCV002032555 uncertain significance not provided 2021-06-07 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 does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33297549, 21356526, 27535533)
Fulgent Genetics, Fulgent Genetics RCV002477901 SCV002796312 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-12-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001723374 SCV003525597 uncertain significance not provided 2022-04-22 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. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 703 of the WFS1 protein (p.Arg703His). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with non-syndromic deafness (PMID: 21356526, 33297549). ClinVar contains an entry for this variant (Variation ID: 1297606). 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.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001723374 SCV001958984 likely pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001723374 SCV001971837 likely pathogenic not provided no assertion criteria provided clinical testing

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