Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001051613 | SCV001215779 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2022-08-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 41014). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 17143884; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 30 of the MPZ protein (p.Ile30Thr). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ile30 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7694726). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects MPZ function (PMID: 20461396). |
| Gene |
RCV000033911 | SCV000057827 | not provided | Charcot-Marie-Tooth disease type 1B | no assertion provided | literature only | ||
| Inherited Neuropathy Consortium | RCV000789434 | SCV000928789 | uncertain significance | Dejerine-Sottas disease | no assertion criteria provided | literature only |