Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000824269 | SCV000965162 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2022-09-10 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MPZ-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 138 of the MPZ protein (p.Lys138Glu). ClinVar contains an entry for this variant (Variation ID: 665891). 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 not expected to disrupt MPZ protein function. |
| Gene |
RCV004720015 | SCV005326045 | likely pathogenic | not provided | 2023-11-29 | criteria provided, single submitter | clinical testing | Observed in an patient with childhood onset MPZ-related disorder including optic nerve atrophy in the published literature (PMID: 34060176); Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26310628, 20461396, 34060176) |