ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2513C>T (p.Pro838Leu)

gnomAD frequency: 0.00001  dbSNP: rs374704428
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
GeneDx RCV001768196 SCV002008645 uncertain significance not provided 2020-01-03 criteria provided, single submitter clinical testing Observed with a second WFS1 variant in a patient with diabetes, optic atrophy and ataxia in the published literature (Cano et al., 2007); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 17568405)
Labcorp Genetics (formerly Invitae), Labcorp RCV001768196 SCV003525768 uncertain significance not provided 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 838 of the WFS1 protein (p.Pro838Leu). This variant is present in population databases (rs374704428, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive Wolfram syndrome (PMID: 17568405). ClinVar contains an entry for this variant (Variation ID: 1317630). 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.
Fulgent Genetics, Fulgent Genetics RCV005038307 SCV005667580 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-05-18 criteria provided, single submitter clinical testing

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.