Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002396696 | SCV002696137 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-08-10 | criteria provided, single submitter | clinical testing | The p.A464V variant (also known as c.1391C>T), located in coding exon 4 of the SKI gene, results from a C to T substitution at nucleotide position 1391. The alanine at codon 464 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003774301 | SCV004683466 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-03-02 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs755404233, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 464 of the SKI protein (p.Ala464Val). This variant has not been reported in the literature in individuals affected with SKI-related conditions. 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: 1771562). |