Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670029 | SCV000794840 | likely pathogenic | Charlevoix-Saguenay spastic ataxia | 2017-10-17 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001855535 | SCV002147683 | pathogenic | Spastic paraplegia | 2020-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 272 of the SACS protein (p.Arg272His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs745907077, ExAC 0.001%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg272 amino acid residue in SACS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19892370, 30901567). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is expected to disrupt SACS protein function. This variant has been observed in individual(s) with clinical features of spastic ataxia of Charlevoix-Saguenay (ARSACS) (PMID: 23338241, 26288984). ClinVar contains an entry for this variant (Variation ID: 554404). |
| Baylor Genetics | RCV000670029 | SCV004210024 | likely pathogenic | Charlevoix-Saguenay spastic ataxia | 2023-02-23 | criteria provided, single submitter | clinical testing |