Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000555329 | SCV000637291 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 648 of the SKI protein (p.Arg648Gly). This variant is present in population databases (rs555623960, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SKI-related conditions. ClinVar contains an entry for this variant (Variation ID: 463401). 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. |
| Ambry Genetics | RCV002314977 | SCV000739642 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-12-12 | criteria provided, single submitter | clinical testing | The p.R648G variant (also known as c.1942C>G), located in coding exon 6 of the SKI gene, results from a C to G substitution at nucleotide position 1942. The arginine at codon 648 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly 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. |
| Gene |
RCV001560385 | SCV001782791 | uncertain significance | not provided | 2022-09-12 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| ARUP Laboratories, |
RCV000555329 | SCV004564447 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-03-02 | criteria provided, single submitter | clinical testing | The SKI c.1942C>G; p.Arg648Gly variant (rs555623960), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 463401). This variant is found in the general population with an overall allele frequency of 0.004% (8/220634 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.808). Due to limited information, the clinical significance of this variant is uncertain at this time. |