Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Beijing Key Laboratry for Genetics of Birth Defects, |
RCV000789474 | SCV001739482 | likely pathogenic | Dejerine-Sottas disease | 2020-02-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002536917 | SCV003523891 | pathogenic | Charcot-Marie-Tooth disease, type I | 2022-06-18 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 127 of the MPZ protein (p.Cys127Tyr). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys127 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33825325; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 637350). This variant is also known as Cys98Tyr. This missense change has been observed in individual(s) with Déjérine-Sottas syndrome and/or MPZ-related conditions (PMID: 9888385, 10084540, 34539730). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). |
Inherited Neuropathy Consortium | RCV000789474 | SCV000928830 | uncertain significance | Dejerine-Sottas disease | no assertion criteria provided | literature only |