Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000707149 | SCV000836232 | uncertain significance | Shprintzen-Goldberg syndrome | 2018-05-30 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SKI-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with tyrosine at codon 276 of the SKI protein (p.Phe276Tyr). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and tyrosine. |
Ambry Genetics | RCV002424723 | SCV002681460 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-10-29 | criteria provided, single submitter | clinical testing | The p.F276Y variant (also known as c.827T>A), located in coding exon 1 of the SKI gene, results from a T to A substitution at nucleotide position 827. The phenylalanine at codon 276 is replaced by tyrosine, an amino acid with highly similar properties. 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. |