Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001221568 | SCV001393623 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-12-09 | 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. ClinVar contains an entry for this variant (Variation ID: 949968). This variant has not been reported in the literature in individuals affected with SKI-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 188 of the SKI protein (p.Ala188Thr). 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 | RCV002348740 | SCV002654218 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-07-10 | criteria provided, single submitter | clinical testing | The p.A188T variant (also known as c.562G>A), located in coding exon 1 of the SKI gene, results from a G to A substitution at nucleotide position 562. The alanine at codon 188 is replaced by threonine, an amino acid with 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. |