ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2107C>T (p.Arg703Cys)

gnomAD frequency: 0.00004  dbSNP: rs201888856
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV001730049 SCV001976817 pathogenic Wolfram syndrome 1 2021-10-05 criteria provided, single submitter clinical testing PM1, PM2, PM5, PP3, PP5
Labcorp Genetics (formerly Invitae), Labcorp RCV002538697 SCV003240865 uncertain significance not provided 2023-12-01 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 703 of the WFS1 protein (p.Arg703Cys). This variant is present in population databases (rs201888856, gnomAD 0.02%). This missense change has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 22662265). ClinVar contains an entry for this variant (Variation ID: 1299576). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
GeneDx RCV002538697 SCV003924711 uncertain significance not provided 2022-10-11 criteria provided, single submitter clinical testing Also reported as a heterozygous variant in one family with diabetes; however, this variant did not segregate with all the affected individuals (Johansson et al., 2012); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25255707, 23903355, 22662265, 35452662)
Fulgent Genetics, Fulgent Genetics RCV005038283 SCV005667537 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-05-20 criteria provided, single submitter clinical testing

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