Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000490080 | SCV000577262 | uncertain significance | not provided | 2017-04-06 | criteria provided, single submitter | clinical testing | The A4V variant of uncertain significance in the SKI gene has not been published as pathogenic or been reported as benign to our knowledge. Data from control individuals was not available to assess whether A4V may be a common benign variant in the general population. However, the A4V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. |
| Invitae | RCV000703987 | SCV000832919 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-09-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 426734). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt SKI protein function. This variant has not been reported in the literature in individuals affected with SKI-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 4 of the SKI protein (p.Ala4Val). |