Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000201185 | SCV000255805 | likely pathogenic | Charcot-Marie-Tooth disease, type IA | 2015-08-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001206556 | SCV001377868 | likely pathogenic | Charcot-Marie-Tooth disease, type I | 2019-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with threonine at codon 79 of the PMP22 protein (p.Ser79Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). 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. This variant disrupts the p.Ser79 amino acid residue in PMP22. Other variants that disrupt this residue have been observed in individuals with PMP22-related conditions (PMID: 8510709, 9452053), which suggests that this may be a clinically significant amino acid residue. 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"). This variant has been observed to be de novo in an individual affected with Dejerine–Sottas neuropathy (PMID: 22006697). ClinVar contains an entry for this variant (Variation ID: 217236). |