Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002535807 | SCV003441723 | pathogenic | Charcot-Marie-Tooth disease, type I | 2022-07-14 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 72 of the PMP22 protein (p.Ser72Pro). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser72 amino acid residue in PMP22. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8275092, 9004143, 9585367, 10399754, 11314784). 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 expected to disrupt PMP22 protein function. ClinVar contains an entry for this variant (Variation ID: 637384). This variant is also known as T>C transition at nucleotide 284 and proline substitution for serine at amino acid position 79. This missense change has been observed in individual(s) with Dejerine-Sottas syndrome (PMID: 9452053, 10093067, 11139264). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). |
| Inherited Neuropathy Consortium | RCV000789526 | SCV000928882 | uncertain significance | Dejerine-Sottas disease | no assertion criteria provided | literature only |