ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1015G>A (p.Asp339Asn)

gnomAD frequency: 0.00001  dbSNP: rs772392224
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199397 SCV000252481 likely benign not specified 2014-02-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000199397 SCV000272906 uncertain significance not specified 2015-07-20 criteria provided, single submitter clinical testing The p.Asp339Asn variant in WFS1 has not been previously reported in individuals with hearing loss, but has been identified in 1/66734 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs77 2392224). Computational prediction tools and conservation analysis do not provid e strong support for or against an impact to the protein. In summary, the clinic al significance of the p.Asp339Asn variant is uncertain.
Invitae RCV001853207 SCV002303925 uncertain significance not provided 2022-09-27 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 not expected to disrupt WFS1 protein function. ClinVar contains an entry for this variant (Variation ID: 215354). This missense change has been observed in individual(s) with autosomal dominant deafness (PMID: 32382995). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 339 of the WFS1 protein (p.Asp339Asn).
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002509293 SCV002817336 likely 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 rs772392224 in Wolfram's syndrome yet.

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