Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Genetics Laboratory, |
RCV001173697 | SCV001336810 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV001224917 | SCV001397144 | pathogenic | Charcot-Marie-Tooth disease, type I | 2023-10-12 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 63 of the MPZ protein (p.Ser63Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 8835320, 15050444, 17294201). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 14177). 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 not expected to disrupt MPZ protein function. Experimental studies have shown that this missense change affects MPZ function (PMID: 20461396). This variant disrupts the p.Ser63 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7506095, 16495463, 20937820). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000015240 | SCV000035499 | pathogenic | Charcot-Marie-Tooth disease type 1B | 1995-12-01 | no assertion criteria provided | literature only |