Total submissions: 3
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. |
Gene |
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 |