ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1549C>T (p.Arg517Cys)

gnomAD frequency: 0.00006  dbSNP: rs371911218
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001902943 SCV002159165 uncertain significance not provided 2023-01-24 criteria provided, single submitter clinical testing 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: 1396272). This missense change has been observed in individual(s) with Wolfram syndrome (PMID: 28432734). This variant is present in population databases (rs371911218, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 517 of the WFS1 protein (p.Arg517Cys). 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 RCV002503521 SCV002814044 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-02-09 criteria provided, single submitter clinical testing
Laboratory of Prof. Karen Avraham, Tel Aviv University RCV004698355 SCV005199914 likely pathogenic Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6 2024-08-20 criteria provided, single submitter research The p.(Arg517Cys) variant has been detected together with the p.(Arg558His) variant in an individual with moderate-to-profound HL. The two variants might be in compound heteterozygosity but also if they are in cis, it is probably the cause of deafness as the p.(Arg517Cys) variant has been reported as dominant (PMID: 28432734).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.