ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1219C>T (p.His407Tyr)

gnomAD frequency: 0.00004  dbSNP: rs151244358
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Total submissions: 4
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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 RCV000152670 SCV000202031 uncertain significance not specified 2013-10-11 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The His407Tyr varia nt in WFS1 has not been reported in individuals with hearing loss, but has been identified in 0.04% (2/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs151244358). Compu tational analyses (biochemical amino acid properties, conservation, AlignGVGD, P olyPhen2, and SIFT) suggest that the His407Tyr variant may not impact the protei n, though this information is not predictive enough to rule out pathogenicity. I n summary, the clinical significance of this variant cannot be determined with c ertainty; however based upon the computational data, we would lean towards a mor e likely benign role.
Invitae RCV001308356 SCV001497803 uncertain significance not provided 2022-10-05 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: 166583). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs151244358, gnomAD 0.02%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 407 of the WFS1 protein (p.His407Tyr).
Fulgent Genetics, Fulgent Genetics RCV002505159 SCV002816264 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-09-11 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002509252 SCV002817352 likely benign 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 rs151244358 in Wolfram's syndrome yet.

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