Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000235645 | SCV000293625 | uncertain significance | not provided | 2023-09-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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; Has not been previously published as pathogenic or benign to our knowledge; located within Cytoplasmic topological domain per Lee YC, 2010, Sanmaneechai O, 2015; This variant is associated with the following publications: (PMID: 20461396, 26310628) |
| Invitae | RCV001341686 | SCV001535569 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2023-05-31 | 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 not expected to disrupt MPZ protein function. ClinVar contains an entry for this variant (Variation ID: 246180). This missense change has been observed in individual(s) with clinical features of MPZ-related conditions (Invitae). 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 199 of the MPZ protein (p.Lys199Glu). |