ClinVar

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 82 of the MPZ protein (p.Tyr82Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth (CMT) disease type 1 and Déjérine-Sottas syndrome (PMID: 7505151, 9633821, 11545686, 11835375, 12402337, 26310628). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 549681). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MPZ protein function with a positive predictive value of 80%. This variant disrupts the p.Tyr82 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7505151, 11545686, 11835375, 12402337, 26310628). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.