Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001366179 | SCV001562474 | uncertain significance | Shprintzen-Goldberg syndrome | 2020-08-03 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with threonine at codon 352 of the SKI protein (p.Pro352Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs755862763, ExAC 0.02%). This variant has not been reported in the literature in individuals with SKI-related conditions. 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. |
| Ambry Genetics | RCV002404874 | SCV002710802 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-27 | criteria provided, single submitter | clinical testing | The p.P352T variant (also known as c.1054C>A), located in coding exon 2 of the SKI gene, results from a C to A substitution at nucleotide position 1054. The proline at codon 352 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |