ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.437G>A (p.Arg146His)

gnomAD frequency: 0.00011  dbSNP: rs34446752
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001755690 SCV002005304 uncertain significance not provided 2024-12-02 criteria provided, single submitter clinical testing Reported in an individual with hearing loss in published literature (PMID: 38400873); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 38400873)
Labcorp Genetics (formerly Invitae), Labcorp RCV001755690 SCV002172994 uncertain significance not provided 2024-06-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 146 of the WFS1 protein (p.Arg146His). This variant is present in population databases (rs34446752, gnomAD 0.01%). 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: 1319042). 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. 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.
PreventionGenetics, part of Exact Sciences RCV004528533 SCV004107239 uncertain significance WFS1-related disorder 2022-12-21 criteria provided, single submitter clinical testing The WFS1 c.437G>A variant is predicted to result in the amino acid substitution p.Arg146His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.010% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-6290835-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen RCV001755690 SCV004147629 uncertain significance not provided 2022-07-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV004681249 SCV005174961 uncertain significance Inborn genetic diseases 2024-05-29 criteria provided, single submitter clinical testing The c.437G>A (p.R146H) alteration is located in exon 4 (coding exon 3) of the WFS1 gene. This alteration results from a G to A substitution at nucleotide position 437, causing the arginine (R) at amino acid position 146 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005038312 SCV005664677 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-06-21 criteria provided, single submitter clinical testing

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