Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000708326 | SCV000837436 | pathogenic | Hereditary spastic paraplegia 4 | 2021-08-04 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 10-16 of the SPAST gene. This variant would be expected to be in-frame, preserving the integrity of the reading frame. A similar copy number variant has been observed in individuals with hereditary spastic paraplegia (PMID: 17098887, 25065914, 25454648). This variant disrupts the p.Leu426 amino acid residue in SPAST. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10699187, 11809724, 11843700, 15841487, 20718791, 20932283, 22960362). 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. |