ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.101T>C (p.Met34Thr) (rs1060500998)

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 RCV000467465 SCV000544768 pathogenic Charcot-Marie-Tooth Neuropathy X 2016-08-16 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 34 of the GJB1 protein (p.Met34Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple individuals affected with CMTX (PMID: 9401007. 11571214) and has been observed to co-segregate with disease in an affected family (PMID: 8829637). Experimental studies in Xenopus oocytes have shown that this missense change affects the electrophysiological properties of the channel encoded by GJB1, known as Connexin 32 in the literature (PMID: 9354338). Additional experiments in HeLa cells found that this missense change alters the sub-cellular localization of Connexin 32 (PMID: 12460545). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789955 SCV000929340 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.