Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001214022 | SCV001385685 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-07-11 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 943761). 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 glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 551 of the SKI protein (p.Gly551Cys). |
| Ambry Genetics | RCV002402637 | SCV002704676 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-11-07 | criteria provided, single submitter | clinical testing | The p.G551C variant (also known as c.1651G>T), located in coding exon 5 of the SKI gene, results from a G to T substitution at nucleotide position 1651. The glycine at codon 551 is replaced by cysteine, an amino acid with highly dissimilar 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. |