Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002401410 | SCV002712113 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-11-19 | criteria provided, single submitter | clinical testing | The p.L581V variant (also known as c.1741C>G), located in coding exon 5 of the SKI gene, results from a C to G substitution at nucleotide position 1741. The leucine at codon 581 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003097201 | SCV003484268 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-10-13 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 581 of the SKI protein (p.Leu581Val). This variant has not been reported in the literature in individuals affected with SKI-related conditions. 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. |