Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000411155 | SCV000486961 | likely pathogenic | Charlevoix-Saguenay spastic ataxia | 2016-09-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003750787 | SCV004558177 | pathogenic | Spastic paraplegia | 2023-09-21 | criteria provided, single submitter | clinical testing | This variant disrupts a region of the SACS protein in which other variant(s) (p.Asn4549Asp) have been determined to be pathogenic (PMID: 15156359, 21507954). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 371392). This variant has not been reported in the literature in individuals affected with SACS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn3750Thrfs*8) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 830 amino acid(s) of the SACS protein. |