Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000470689 | SCV000552943 | pathogenic | Charcot-Marie-Tooth disease, type I | 2023-06-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser78 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7527371, 9633821, 18347322). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 411669). This missense change has been observed in individuals with autosomal dominant Charcot-Marie-Tooth disease (PMID: 12707985; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 78 of the MPZ protein (p.Ser78Trp). |
Athena Diagnostics Inc | RCV001289097 | SCV001476688 | likely pathogenic | not provided | 2020-01-13 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data is high quality. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. |
Preventiongenetics, |
RCV003409638 | SCV004110977 | likely pathogenic | MPZ-related condition | 2023-03-15 | criteria provided, single submitter | clinical testing | The MPZ c.233C>G variant is predicted to result in the amino acid substitution p.Ser78Trp. This variant was reported in an individual with a personal and family history of Charcot-Marie-Tooth disease, type 1B (Kakar et al. 2003. PubMed ID: 12707985). A different amino acid substitution (p.Ser78Leu) has also been reported to be pathogenic for Charcot-Marie-Tooth disease, type 1B (Nelis et al. 1994. PubMed ID: 7527371). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. |
Inherited Neuropathy Consortium | RCV000789070 | SCV000928419 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |