Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002387267 | SCV002689257 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-02-11 | criteria provided, single submitter | clinical testing | The p.P328L variant (also known as c.983C>T), located in coding exon 2 of the SKI gene, results from a C to T substitution at nucleotide position 983. The proline at codon 328 is replaced by leucine, 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. |
| Gene |
RCV002463206 | SCV002756608 | uncertain significance | not provided | 2022-05-15 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV003631254 | SCV004518237 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-08-04 | 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) 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: 1768359). This variant has not been reported in the literature in individuals affected with SKI-related conditions. This variant is present in population databases (rs777251951, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 328 of the SKI protein (p.Pro328Leu). |