Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000818403 | SCV000959014 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2021-07-13 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Pro132 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID: 9452099, 20456450), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 661067). This variant has been observed in individuals with clinical features of Charcot-Marie-Tooth disease (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 132 of the MPZ protein (p.Pro132Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |