Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000532859 | SCV000637272 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 357 of the SKI protein (p.Arg357Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with thoracic aortic aneurysm or dissection (PMID: 29543232). ClinVar contains an entry for this variant (Variation ID: 463392). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Gene |
RCV001770430 | SCV001992460 | uncertain significance | not provided | 2023-10-10 | criteria provided, single submitter | clinical testing | Has been reported as a variant of uncertain significance in an individual with ascending aortic aneurysm (Weerakkody et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29543232) |
| Ambry Genetics | RCV002413501 | SCV002717455 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-05-12 | criteria provided, single submitter | clinical testing | The p.R357W variant (also known as c.1069C>T), located in coding exon 2 of the SKI gene, results from a C to T substitution at nucleotide position 1069. The arginine at codon 357 is replaced by tryptophan, an amino acid with dissimilar properties. This variant has been detected in an individual with ascending aortic aneurysm (Weerakkody R et al. Genet Med. 2018 11;20(11):1414-1422). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |