ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.535G>A (p.Ala179Thr)

gnomAD frequency: 0.00001  dbSNP: rs776685250
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000214251 SCV000272923 uncertain significance not specified 2015-08-12 criteria provided, single submitter clinical testing The p.Ala179Thr variant in WFS1 has not been previously reported in individuals with hearing loss or Wolfram syndrome, but has been identified in 2/8632 East As ian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs776685250). Computational prediction tools and conservation a nalyses do not provide strong support for or against an impact to the protein. I n summary, the clinical significance of the p.Ala179Thr variant is uncertain.
Fulgent Genetics, Fulgent Genetics RCV000765773 SCV000897162 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2018-10-31 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002509054 SCV002773844 uncertain risk allele Wolfram syndrome 1 criteria provided, single submitter research Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs776685250 in Wolfram's syndrome yet.
Labcorp Genetics (formerly Invitae), Labcorp RCV002519659 SCV003272840 uncertain significance not provided 2022-03-10 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) performed at Invitae indicates that this missense variant is expected to disrupt WFS1 protein function. ClinVar contains an entry for this variant (Variation ID: 229647). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs776685250, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 179 of the WFS1 protein (p.Ala179Thr).
CeGaT Center for Human Genetics Tuebingen RCV002519659 SCV003916883 uncertain significance not provided 2023-03-01 criteria provided, single submitter clinical testing
GeneDx RCV002519659 SCV004167854 uncertain significance not provided 2023-10-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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