ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1072G>C (p.Val358Leu)

gnomAD frequency: 0.00004  dbSNP: rs969150051
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001558648 SCV001780642 uncertain significance not provided 2019-06-05 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001558648 SCV002114098 uncertain significance not provided 2024-12-05 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 358 of the WFS1 protein (p.Val358Leu). This variant is present in population databases (no rsID available, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1195529). 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 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV005023191 SCV005660216 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-02-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005057510 SCV005726153 uncertain significance not specified 2024-11-20 criteria provided, single submitter clinical testing Variant summary: WFS1 c.1072G>C (p.Val358Leu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251434 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in WFS1 causing Wolfram Syndrome 1, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1072G>C in individuals affected with Wolfram Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1195529). Based on the evidence outlined above, the variant was classified as uncertain significance.

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