Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002512923 | SCV003441655 | pathogenic | Charcot-Marie-Tooth disease, type I | 2022-08-27 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Ser79 amino acid residue in PMP22. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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. 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. ClinVar contains an entry for this variant (Variation ID: 8429). This missense change has been observed in individual(s) with Charcot-Marie-Tooth Type 1 (PMID: 8510709). 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 79 of the PMP22 protein (p.Ser79Cys). |
| OMIM | RCV000008941 | SCV000029151 | pathogenic | Charcot-Marie-Tooth disease, type IA | 1993-07-08 | no assertion criteria provided | literature only |