Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003631457 | SCV004385724 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 12 of the SKI protein (p.Gln12His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SKI-related conditions. 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. 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 | RCV004371551 | SCV005019742 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-03-14 | criteria provided, single submitter | clinical testing | The p.Q12H variant (also known as c.36G>C), located in coding exon 1 of the SKI gene, results from a G to C substitution at nucleotide position 36. The glutamine at codon 12 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |