ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.547C>T (p.Arg183Cys)

dbSNP: rs863224471
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000197033 SCV000253768 pathogenic Charcot-Marie-Tooth Neuropathy X 2023-11-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 183 of the GJB1 protein (p.Arg183Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 9187667, 11271367, 25429913, 28469099). ClinVar contains an entry for this variant (Variation ID: 216039). 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 expected to disrupt GJB1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects GJB1 function (PMID: 1211842, 27844031). This variant disrupts the p.Arg183 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9187667, 12111842, 15719046, 27027447, 27844031). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000235360 SCV000293450 pathogenic not provided 2021-10-29 criteria provided, single submitter clinical testing Reported previously in association with CMTX in affected males and females (Bone et al., 1997, Hahn et al., 2001, Bort et al., 1997); Not observed at significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24444136, 21871435, 9361298, 11271367, 12111842, 25429913, 12457340, 9187667, 31211173, 32376792, 34060689, 32903794, 30952033, 30042657)
Athena Diagnostics RCV000235360 SCV000613490 likely pathogenic not provided 2017-12-29 criteria provided, single submitter clinical testing
NeuroMeGen, Hospital Clinico Santiago de Compostela RCV000754745 SCV000882635 likely pathogenic Charcot-Marie-Tooth disease X-linked dominant 1 2018-10-08 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000235360 SCV004226251 pathogenic not provided 2022-10-14 criteria provided, single submitter clinical testing PP3, PM1, PM2, PS3, PS4
Inherited Neuropathy Consortium RCV000789836 SCV000929220 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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.