ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.472G>A (p.Glu158Lys)

gnomAD frequency: 0.00001  dbSNP: rs567563179
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001899046 SCV002173351 likely pathogenic not provided 2024-12-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 158 of the WFS1 protein (p.Glu158Lys). This variant is present in population databases (rs567563179, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of Wolfram syndrome (PMID: 19042979, 31658956, 33841295). ClinVar contains an entry for this variant (Variation ID: 1404588). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt WFS1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects WFS1 function (PMID: 34848728). 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.
Mendelics RCV002246586 SCV002516172 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005038478 SCV005664681 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-01-22 criteria provided, single submitter clinical testing

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