Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000638178 | SCV000759664 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2023-01-19 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.His39 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14711881, 16844954, 18337304, 26310628). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is not expected to disrupt MPZ protein function. ClinVar contains an entry for this variant (Variation ID: 531695). This missense change has been observed in individual(s) with clinical features of MPZ-related conditions (Invitae). This variant is present in population databases (rs371856018, gnomAD 0.01%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 39 of the MPZ protein (p.His39Arg). |