Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001237899 | SCV001410686 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 423 of the SKI protein (p.Pro423Leu). This variant is present in population databases (rs752779978, gnomAD 0.002%). 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: 963815). 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. 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 | RCV002375256 | SCV002687855 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-05 | criteria provided, single submitter | clinical testing | The p.P423L variant (also known as c.1268C>T), located in coding exon 4 of the SKI gene, results from a C to T substitution at nucleotide position 1268. The proline at codon 423 is replaced by leucine, an amino acid with similar properties. This variant was detected by genome sequencing in an individual with an ophthalmologic phenotype rather than a connective tissue phenotype; however details were limited (Kasak L et al. Hum. Mutat., 2019 09;40:1373-1391). This amino acid position is highly 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. |
| Gene |
RCV002462860 | SCV002757619 | uncertain significance | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing | Reported in a patient with an ophthalmologic disorder from a cohort of children with undiagnosed diseases who underwent whole genome sequencing (Kasak et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31322791) |