Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001243834 | SCV001417017 | uncertain significance | Shprintzen-Goldberg syndrome | 2020-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 373 of the SKI protein (p.Arg373His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs768924434, ExAC 0.002%). This variant has not been reported in the literature in individuals with SKI-related conditions. 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"). 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 | RCV002436958 | SCV002749859 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-02-14 | criteria provided, single submitter | clinical testing | The p.R373H variant (also known as c.1118G>A), located in coding exon 3 of the SKI gene, results from a G to A substitution at nucleotide position 1118. The arginine at codon 373 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |