Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000554187 | SCV000636248 | pathogenic | Charcot-Marie-Tooth disease, type I | 2020-02-04 | criteria provided, single submitter | clinical testing | 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 MPZ protein function. This variant has been observed in individual(s) with autosomal dominant Charcot-Marie-Tooth disease (PMID: 31315766, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 462796). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 132 of the MPZ protein (p.Pro132Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. |
| Gene |
RCV003233703 | SCV003931023 | pathogenic | not provided | 2022-12-04 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31315766, 26310628, 20461396, 33825325, 24077912) |