ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.515C>T (p.Pro172Leu) (rs1555937218)

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 RCV000559484 SCV000658914 pathogenic Charcot-Marie-Tooth Neuropathy X 2017-04-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 172 of the GJB1 protein (p.Pro172Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with Charcot-Marie-Tooth disease, type X1 (CMTX1)(PMID: 9856562, 27098783, 21692908). It has also been reported to segregate with disease in a family affected with CMTX1 (PMID: 9633821). This variant is also known as c.577 C>T in the literature. 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. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789937 SCV000929322 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.