Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002649495 | SCV002975775 | uncertain significance | Shprintzen-Goldberg syndrome | 2024-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 622 of the SKI protein (p.Glu622Asp). This variant is present in population databases (rs748886393, gnomAD 0.001%). 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: 1932726). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SKI protein function with a negative predictive value of 95%. 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 | RCV003357962 | SCV004053801 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-09-08 | criteria provided, single submitter | clinical testing | The p.E622D variant (also known as c.1866G>C), located in coding exon 6 of the SKI gene, results from a G to C substitution at nucleotide position 1866. The glutamic acid at codon 622 is replaced by aspartic 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. |