Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003511973 | SCV004299660 | uncertain significance | Hereditary spastic paraplegia 2 | 2023-06-10 | criteria provided, single submitter | clinical testing | This variant is also known as p.Leu223Pro. This missense change has been observed in individual(s) with Pelizaeus-Merzbacher diseae (PMID: 1384324). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 224 of the PLP1 protein (p.Leu224Pro). 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.Leu224 amino acid residue in PLP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23347225, 26786043; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects PLP1 function (PMID: 22016529). 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 PLP1 protein function. ClinVar contains an entry for this variant (Variation ID: 11080). |
| OMIM | RCV000011829 | SCV000032062 | pathogenic | Pelizaeus-Merzbacher disease | 1992-10-01 | no assertion criteria provided | literature only |