Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000442849 | SCV000536583 | uncertain significance | not provided | 2018-01-17 | criteria provided, single submitter | clinical testing | The V596L variant has not beenpublished as pathogenic or been reported as benign to our knowledge. It is not observed in the ExAC dataset (Lek etal., 2016). The V596L substitution occurs at a position that is conserved across species. However, this variant is aconservative amino acid substitution, which is not likely to impact secondary protein structure as these residues sharesimilar properties. In addition, in silico analysis is inconsistent in its predictions as to whether or not the variant isdamaging to the protein structure/function. |
| Invitae | RCV002526365 | SCV003315681 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-07-06 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 393207). 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 valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 596 of the SKI protein (p.Val596Leu). |