Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001390412 | SCV001592139 | pathogenic | Charcot-Marie-Tooth disease, type I | 2022-08-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Thr65 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID: 12402337, 15036333, 15050444, 20456450, 31211173), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 637928). This missense change has been observed in individual(s) with MPZ-related conditions (PMID: 20456450). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 65 of the MPZ protein (p.Thr65Asn). |
| Mendelics | RCV002249496 | SCV002517326 | likely pathogenic | Charcot-Marie-Tooth disease type 1B | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Inherited Neuropathy Consortium | RCV000790308 | SCV000929716 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |