Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001383518 | SCV001582669 | pathogenic | Spastic paraplegia | 2023-07-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu3714*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 866 amino acid(s) of the SACS protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SACS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1071138). This variant disrupts a region of the SACS protein in which other variant(s) (p.Asn4549Asp, p.Glu4510Argfs*4) have been determined to be pathogenic (PMID: 15156359, 21507954, 29915382). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469390 | SCV002766373 | likely pathogenic | Charlevoix-Saguenay spastic ataxia | 2022-11-17 | criteria provided, single submitter | clinical testing | Variant summary: SACS c.11136delA (p.Leu3714X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory and associated with Spastic Ataxia of Charlevoix-Saguenay in HGMD. The variant was absent in 251180 control chromosomes. To our knowledge, no occurrence of c.11136delA in individuals affected with Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV002469390 | SCV004202315 | likely pathogenic | Charlevoix-Saguenay spastic ataxia | 2022-01-21 | criteria provided, single submitter | clinical testing |