ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2134A>G (p.Ile712Val)

gnomAD frequency: 0.00008  dbSNP: rs574657627
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001295108 SCV001484019 uncertain significance not provided 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 712 of the WFS1 protein (p.Ile712Val). This variant is present in population databases (rs574657627, 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: 999148). 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 with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002499541 SCV002814873 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-05-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV002541826 SCV003699751 uncertain significance Inborn genetic diseases 2021-05-21 criteria provided, single submitter clinical testing The c.2134A>G (p.I712V) alteration is located in exon 8 (coding exon 7) of the WFS1 gene. This alteration results from a A to G substitution at nucleotide position 2134, causing the isoleucine (I) at amino acid position 712 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV003128199 SCV003804225 uncertain significance 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 rs574657627 in Wolfram's syndrome yet.
GeneDx RCV001295108 SCV005079257 uncertain significance not provided 2023-12-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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