Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003581727 | SCV004293778 | pathogenic | Charcot-Marie-Tooth disease, type I | 2022-10-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 637783). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 25429913). 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 tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 82 of the MPZ protein (p.Tyr82Ser). 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. For these reasons, this variant has been classified as Pathogenic. 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: 16543539). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |
Inherited Neuropathy Consortium | RCV000790097 | SCV000929487 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |