Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000638174 | SCV000759660 | uncertain significance | Charcot-Marie-Tooth disease, type I | 2022-07-26 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 531691). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease, type 1 (PMID: 9452099). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 58 of the MPZ protein (p.Val58Phe). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.Val58 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID: 15050444), which suggests that this may be a clinically significant amino acid residue. |
| Inherited Neuropathy Consortium | RCV000789480 | SCV000928836 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |