Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001234587 | SCV001407241 | uncertain significance | Hereditary spastic paraplegia 4 | 2023-07-27 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SPAST-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 495 of the SPAST protein (p.Ala495Ser). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 960966). 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 SPAST protein function. This variant disrupts the p.Ala495 amino acid residue in SPAST. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31157359, 32989326). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Paris Brain Institute, |
RCV001234587 | SCV001450994 | pathogenic | Hereditary spastic paraplegia 4 | criteria provided, single submitter | clinical testing |