ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2194C>T (p.Arg732Cys)

gnomAD frequency: 0.00001  dbSNP: rs71526458
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Personalized Diabetes Medicine Program, University of Maryland School of Medicine RCV000445445 SCV000537020 uncertain significance Monogenic diabetes 2016-06-03 criteria provided, single submitter research ACMG Criteria: PP3
Labcorp Genetics (formerly Invitae), Labcorp RCV001857736 SCV002280010 likely pathogenic not provided 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 732 of the WFS1 protein (p.Arg732Cys). This variant is present in population databases (rs71526458, gnomAD 0.02%). This missense change has been observed in individual(s) with autosomal recessive Wolfram syndrome and/or clinical features of WFS1-related conditions (PMID: 32179840, 34404380, 34573359, 35469785). ClinVar contains an entry for this variant (Variation ID: 215396). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002500616 SCV002814092 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-03-24 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001857736 SCV004226102 likely pathogenic not provided 2023-03-23 criteria provided, single submitter clinical testing PP3, PM2, PM3_supporting, PS4_moderate
Genomics England Pilot Project, Genomics England RCV001542532 SCV001760142 pathogenic Type 2 diabetes mellitus no assertion criteria provided clinical testing

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