Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519608 | SCV000620676 | uncertain significance | not provided | 2017-09-13 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SACS gene. The c.6485 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.6485 A>G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.6485 A>G may create a cryptic splice donor site which may supplant the natural donor site and lead to abnormal gene splicing; however, in the absence of RNA/functional studies the actual effect of c.6485 A>G on splicing is unknown. If c.6485 A>G does not alter splicing, it will result in the D2162G missense change, which is a non-conservative amino acid substitution that is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Natera, |
RCV001829518 | SCV002086237 | uncertain significance | Charlevoix-Saguenay spastic ataxia | 2021-05-04 | no assertion criteria provided | clinical testing |