Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002311100 | SCV000319953 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-01-27 | criteria provided, single submitter | clinical testing | The p.P322S variant (also known as c.964C>T), located in coding exon 1 of the SKI gene, results from a C to T substitution at nucleotide position 964. The proline at codon 322 is replaced by serine, an amino acid with some similar properties. This amino acid position is well conserved in available vertebrates and serine is the reference amino acid in a few lower species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV000803496 | SCV000943371 | uncertain significance | Shprintzen-Goldberg syndrome | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 322 of the SKI protein (p.Pro322Ser). This variant is present in population databases (rs779317743, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SKI-related conditions. ClinVar contains an entry for this variant (Variation ID: 264199). 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 with a negative predictive value of 95%. 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. |
| Gene |
RCV001548131 | SCV001767988 | uncertain significance | not provided | 2020-06-01 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 264199; Landrum et al., 2016) |
| Prevention |
RCV003939921 | SCV004752220 | uncertain significance | SKI-related disorder | 2024-02-12 | criteria provided, single submitter | clinical testing | The SKI c.964C>T variant is predicted to result in the amino acid substitution p.Pro322Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0053% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Centre de Biologie Pathologie Génétique, |
RCV001251641 | SCV001427379 | uncertain significance | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing |