Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002315214 | SCV000739640 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-11-01 | criteria provided, single submitter | clinical testing | The p.P198L variant (also known as c.593C>T), located in coding exon 1 of the SKI gene, results from a C to T substitution at nucleotide position 593. The proline at codon 198 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001771836 | SCV002002424 | uncertain significance | not provided | 2020-07-13 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 520171; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| Invitae | RCV002531851 | SCV003512308 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-05-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 520171). This variant has not been reported in the literature in individuals affected with SKI-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 198 of the SKI protein (p.Pro198Leu). 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. |