ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.191G>A (p.Cys64Tyr) (rs1602348897)

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 RCV001065214 SCV001230164 pathogenic Charcot-Marie-Tooth Neuropathy X 2019-01-27 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 64 of the GJB1 protein (p.Cys64Tyr). 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 individuals affected with Charcot-Marie-Tooth disease and has been observed to segregate with disease in a family (PMID: 27862672, 27098783, 24768312, 25883816). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Cys64 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 11437164, 9187667), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789867 SCV000929252 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.