Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002410047 | SCV002714813 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-17 | criteria provided, single submitter | clinical testing | The p.S354I variant (also known as c.1061G>T), located in coding exon 2 of the SKI gene, results from a G to T substitution at nucleotide position 1061. The serine at codon 354 is replaced by isoleucine, an amino acid with dissimilar 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 | RCV003097258 | SCV003465905 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-10-19 | criteria provided, single submitter | clinical testing | 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. 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 serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 354 of the SKI protein (p.Ser354Ile). 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. |