ClinVar

Description

This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 140 of the MPZ protein (p.Ser140Thr). This variant is present in population databases (rs572010627, gnomAD 0.002%). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 12207932, 14711881, 26310628). It has also been observed to segregate with disease in related individuals. This variant is also known as c.752T>A or p.Ser111Thr. ClinVar contains an entry for this variant (Variation ID: 447730). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MPZ protein function. This variant disrupts the p.Ser140 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12207932, 22433810, 24028194). 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.