ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.602G>A (p.Cys201Tyr) (rs1602349730)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001070375 SCV001235601 uncertain significance Charcot-Marie-Tooth Neuropathy X 2019-03-15 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 201 of the GJB1 protein (p.Cys201Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with X-linked Charcot-Marie-Tooth disease (PMID: 12477701). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Cys201 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9452025, 17100997). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Inherited Neuropathy Consortium RCV000789861 SCV000929246 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.