Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001586693 | SCV001820509 | uncertain significance | not provided | 2021-04-14 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function |
| Ambry Genetics | RCV002421221 | SCV002720282 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-07-12 | criteria provided, single submitter | clinical testing | The p.D680E variant (also known as c.2040C>G), located in coding exon 7 of the SKI gene, results from a C to G substitution at nucleotide position 2040. The aspartic acid at codon 680 is replaced by glutamic acid, 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. |
| Fulgent Genetics, |
RCV002495946 | SCV002791075 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-03-09 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002495946 | SCV003476574 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-10-26 | 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) 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. ClinVar contains an entry for this variant (Variation ID: 1215755). This variant has not been reported in the literature in individuals affected with SKI-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 680 of the SKI protein (p.Asp680Glu). |