Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV002249492 | SCV002517327 | likely pathogenic | Charcot-Marie-Tooth disease type 1B | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003581718 | SCV004293783 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2023-06-29 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: 637323). This variant is also known as p.Thr5Ile. This missense change has been observed in individuals with Charcot-Marie-Tooth and/or Charcot-Marie-Tooth disease (PMID: 8797476; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 34 of the MPZ protein (p.Thr34Ile). |
| Inherited Neuropathy Consortium | RCV000789435 | SCV000928790 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |