ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1180G>A (p.Glu394Lys)

gnomAD frequency: 0.00004  dbSNP: rs373146435
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001153040 SCV001314286 uncertain significance Autosomal dominant nonsyndromic hearing loss 6 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001153041 SCV001314287 uncertain significance WFS1-Related Spectrum Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001348921 SCV001543247 uncertain significance not provided 2023-04-28 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 904869). This missense change has been observed in individual(s) with optic neuropathy (PMID: 33841295). This variant is present in population databases (rs373146435, gnomAD 0.1%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 394 of the WFS1 protein (p.Glu394Lys).
GeneDx RCV001348921 SCV002008221 uncertain significance not provided 2022-11-01 criteria provided, single submitter clinical testing Reported in a patient with optic neuropathy in published literature (Charif et al., 2021); clinical information is limited; 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: 26435059, 33841295)
Fulgent Genetics, Fulgent Genetics RCV002480552 SCV002790007 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-07-19 criteria provided, single submitter clinical testing

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