Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000494031 | SCV000583264 | likely pathogenic | not provided | 2024-12-19 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; 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 indicates that this missense variant does not alter protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 26310628, 20461396) |
| Molecular Genetics Laboratory, |
RCV001173700 | SCV001336813 | likely pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Institute of Medical Genetics and Applied Genomics, |
RCV000494031 | SCV001448019 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002527111 | SCV003221931 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2024-05-11 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 145 of the MPZ protein (p.Tyr145Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MPZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 430459). 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%. This variant disrupts the p.Tyr145 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12805115, 12845552). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Mayo Clinic Laboratories, |
RCV000494031 | SCV005408480 | uncertain significance | not provided | 2024-05-20 | criteria provided, single submitter | clinical testing | PM2, PM5 |