Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000544643 | SCV000637296 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-03-25 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt SKI protein function. ClinVar contains an entry for this variant (Variation ID: 463406). 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 687 of the SKI protein (p.Asp687Glu). |
Ambry Genetics | RCV002420411 | SCV002725601 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-07 | criteria provided, single submitter | clinical testing | The p.D687E variant (also known as c.2061C>A), located in coding exon 7 of the SKI gene, results from a C to A substitution at nucleotide position 2061. The aspartic acid at codon 687 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. |