Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001224441 | SCV001396633 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2022-12-23 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Ser54 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID: 10533074), which suggests that this may be a clinically significant amino acid residue. 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 MPZ protein function. ClinVar contains an entry for this variant (Variation ID: 637324). This missense change has been observed in individual(s) with severe Charcot-Marie-Tooth disease (PMID: 10093067, 12090401, 25025039). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 54 of the MPZ protein (p.Ser54Cys). 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. |
| Revvity Omics, |
RCV003130036 | SCV003808911 | uncertain significance | not provided | 2019-06-18 | criteria provided, single submitter | clinical testing | |
| Inherited Neuropathy Consortium | RCV000789437 | SCV000928792 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |