ClinVar Miner

Submissions for variant NM_000304.4(PMP22):c.277G>C (p.Gly93Arg)

dbSNP: rs778693173
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001869223 SCV002159389 uncertain significance Charcot-Marie-Tooth disease, type I 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 93 of the PMP22 protein (p.Gly93Arg). This variant is present in population databases (rs778693173, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 8777804). ClinVar contains an entry for this variant (Variation ID: 637390). 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 PMP22 protein function with a positive predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on PMP22 function (PMID: 10078969, 12901701, 26102530, 33933451). 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.
GeneDx RCV002281130 SCV002569681 uncertain significance not provided 2022-03-02 criteria provided, single submitter clinical testing Published in vitro functional studies demonstrate no significant difference in PMP22 protein function is observed in cells with the p.G93R variant (Naef et al., 1999; Marinko et al., 2021); 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: 32647009, 12901701, 33933451, 32513719, 10330345, 26102530, 15474367, 8777804, 33893233, 10078969)
Inherited Neuropathy Consortium RCV000789533 SCV000928889 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.