Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000558954 | SCV000636237 | pathogenic | Charcot-Marie-Tooth disease, type I | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 35 of the MPZ protein (p.Asp35Asn). This variant is present in population databases (no rsID available, gnomAD 0.005%). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (CMT) (PMID: 20385006, 24053775, 24444136). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 462790). 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 with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Institute Of Human Genetics Munich, |
RCV000995582 | SCV001149841 | pathogenic | Charcot-Marie-Tooth disease type 2I | 2019-10-09 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001093015 | SCV001249790 | pathogenic | not provided | 2020-01-01 | criteria provided, single submitter | clinical testing | |
Inherited Neuropathy Consortium | RCV000790058 | SCV000929448 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |