Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002414932 | SCV002722218 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-04-25 | criteria provided, single submitter | clinical testing | The p.A621T variant (also known as c.1861G>A), located in coding exon 6 of the SKI gene, results from a G to A substitution at nucleotide position 1861. The alanine at codon 621 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |
| Labcorp Genetics |
RCV003097308 | SCV003266859 | uncertain significance | Shprintzen-Goldberg syndrome | 2022-10-25 | 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. 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. 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 621 of the SKI protein (p.Ala621Thr). |