Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002385718 | SCV002691422 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-01 | criteria provided, single submitter | clinical testing | The p.R441Q variant (also known as c.1322G>A), located in coding exon 4 of the SKI gene, results from a G to A substitution at nucleotide position 1322. The arginine at codon 441 is replaced by glutamine, 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. |
Invitae | RCV003103645 | SCV003263292 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-09-16 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. 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 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 441 of the SKI protein (p.Arg441Gln). |
Mayo Clinic Laboratories, |
RCV003481297 | SCV004227715 | uncertain significance | not provided | 2023-04-06 | criteria provided, single submitter | clinical testing | PM2_supporting |