Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001316815 | SCV001507451 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-10-02 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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: 1017638). This variant has not been reported in the literature in individuals affected with SKI-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 102 of the SKI protein (p.Glu102Lys). |
| Ambry Genetics | RCV002447341 | SCV002754119 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-17 | criteria provided, single submitter | clinical testing | The p.E102K variant (also known as c.304G>A), located in coding exon 1 of the SKI gene, results from a G to A substitution at nucleotide position 304. The glutamic acid at codon 102 is replaced by lysine, an amino acid with 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. |