Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489520 | SCV000577301 | uncertain significance | not provided | 2017-04-05 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SKI gene. The V567A variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V567A variant occurs at a position where amino acids with similar properties to valine are tolerated across species. Moreover, this substitution is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Invitae | RCV003631125 | SCV004447280 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 567 of the SKI protein (p.Val567Ala). 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) 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 SKI protein function. ClinVar contains an entry for this variant (Variation ID: 426770). 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). |