Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000199076 | SCV000250671 | uncertain significance | not provided | 2015-03-02 | criteria provided, single submitter | clinical testing | p.Tyr313Cys (Y313C) TAT>TGT: c.938 A>G in exon 1 of the SKI gene (NM_003036.3) A variant of unknown significance has been identified in the SKI gene. The Y313C variant has not been published as a mutation or been reported as a benign polymorphism to our knowledge. The Y313C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved through mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense mutations in nearby residues have been reported, indicating that this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAADV2-1 |
| Ambry Genetics | RCV002444796 | SCV002682424 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-09-11 | criteria provided, single submitter | clinical testing | The p.Y313C variant (also known as c.938A>G), located in coding exon 1 of the SKI gene, results from an A to G substitution at nucleotide position 938. The tyrosine at codon 313 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not 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. |
| Invitae | RCV002515367 | SCV003458039 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-07-17 | 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. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 313 of the SKI protein (p.Tyr313Cys). This variant is not present in population databases (gnomAD no frequency). 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: 213687). 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. |