Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000638887 | SCV000760441 | uncertain significance | Shprintzen-Goldberg syndrome | 2018-06-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with SKI-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 309 of the SKI protein (p.Glu309Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. |
| Ambry Genetics | RCV002448987 | SCV002682456 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-07-07 | criteria provided, single submitter | clinical testing | The p.E309K variant (also known as c.925G>A), located in coding exon 1 of the SKI gene, results from a G to A substitution at nucleotide position 925. The glutamic acid at codon 309 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |