Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668456 | SCV000793063 | uncertain significance | Charlevoix-Saguenay spastic ataxia | 2017-08-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001576889 | SCV001804162 | uncertain significance | not provided | 2022-10-17 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29482223, 26288984) |
Genome- |
RCV000668456 | SCV002026505 | uncertain significance | Charlevoix-Saguenay spastic ataxia | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001868222 | SCV002238295 | pathogenic | Spastic paraplegia | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2703 of the SACS protein (p.Arg2703His). This variant is present in population databases (rs750181262, gnomAD 0.01%). This missense change has been observed in individuals with clinical features of hereditary spastic paraplegia (PMID: 26288984; Invitae). ClinVar contains an entry for this variant (Variation ID: 553081). Advanced 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 at Invitae 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 SACS protein function. This variant disrupts the p.Arg2703 amino acid residue in SACS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16007637, 29277257). 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. |
Baylor Genetics | RCV000668456 | SCV004210023 | likely pathogenic | Charlevoix-Saguenay spastic ataxia | 2024-03-22 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000668456 | SCV002086215 | uncertain significance | Charlevoix-Saguenay spastic ataxia | 2020-08-14 | no assertion criteria provided | clinical testing |