Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000465525 | SCV000550373 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-08-23 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs749507746, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 373 of the SKI protein (p.Arg373Cys). This missense change has been observed in individual(s) with thoracic aortic aneurysm (PMID: 33824467). 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 expected to disrupt SKI protein function. ClinVar contains an entry for this variant (Variation ID: 409970). |
Department of Vascular Biology, |
RCV001374770 | SCV001439487 | uncertain significance | Isolated thoracic aortic aneurysm | 2018-09-01 | criteria provided, single submitter | research | |
Ce |
RCV001532046 | SCV001747426 | uncertain significance | not provided | 2021-03-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001532046 | SCV001791912 | uncertain significance | not provided | 2023-08-07 | criteria provided, single submitter | clinical testing | Has been reported as a variant of uncertain significance in a Chinese patient with TAAD (Li et al., 2021); 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: 33824467) |
Ambry Genetics | RCV002436441 | SCV002750423 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-10-29 | criteria provided, single submitter | clinical testing | The p.R373C variant (also known as c.1117C>T), located in coding exon 3 of the SKI gene, results from a C to T substitution at nucleotide position 1117. The arginine at codon 373 is replaced by cysteine, an amino acid with highly dissimilar 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. |