ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1623T>G (p.Cys541Trp)

gnomAD frequency: 0.00001  dbSNP: rs745712429
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001350530 SCV001544935 uncertain significance not provided 2021-12-15 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: 1046024). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs745712429, gnomAD 0.003%). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 541 of the WFS1 protein (p.Cys541Trp).
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV003127829 SCV003801385 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 rs745712429 in Wolfram's syndrome yet.
Ambry Genetics RCV003284244 SCV003961199 uncertain significance Inborn genetic diseases 2023-05-23 criteria provided, single submitter clinical testing The c.1623T>G (p.C541W) alteration is located in exon 8 (coding exon 7) of the WFS1 gene. This alteration results from a T to G substitution at nucleotide position 1623, causing the cysteine (C) at amino acid position 541 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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