Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001207414 | SCV001378764 | pathogenic | Spastic paraplegia | 2023-04-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SACS protein in which other variant(s) (p.Tyr4538*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 938233). This variant has not been reported in the literature in individuals affected with SACS-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Trp1861*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2719 amino acid(s) of the SACS protein. |
Gene |
RCV002462358 | SCV002757394 | likely pathogenic | not provided | 2022-05-09 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 2719 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |
Baylor Genetics | RCV003469338 | SCV004209886 | likely pathogenic | Charlevoix-Saguenay spastic ataxia | 2023-10-20 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV002462358 | SCV004229951 | pathogenic | not provided | 2023-02-08 | criteria provided, single submitter | clinical testing | This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. |