Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002009750 | SCV002264548 | uncertain significance | Hereditary spastic paraplegia 2 | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 33 of the PLP1 protein (p.Cys33Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary spastic paraplegia and hypomyelinating leukodystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 1479235). 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. This variant disrupts the p.Cys33 amino acid residue in PLP1. Other variant(s) that disrupt this residue have been observed in individuals with PLP1-related conditions (PMID: 15712223, 29451896), which suggests that this may be a clinically significant amino acid residue. 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003136402 | SCV003807776 | uncertain significance | Pelizaeus-Merzbacher disease | 2022-09-16 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 moderated, PM5 moderated, PP3 supporting |