Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000004595 | SCV001419645 | pathogenic | Hereditary spastic paraplegia 3A | 2024-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 259 of the ATL1 protein (p.Ser259Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant hereditary spastic paraplegia (PMID: 11685207, 29907907). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4347). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATL1 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ATL1 function (PMID: 25761634). This variant disrupts the p.Ser259 amino acid residue in ATL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19459885, 29691679). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000004595 | SCV000024769 | pathogenic | Hereditary spastic paraplegia 3A | 2001-11-01 | no assertion criteria provided | literature only |