Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001348169 | SCV001542460 | uncertain significance | Shprintzen-Goldberg syndrome | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with glutamine at codon 81 of the SKI protein (p.Pro81Gln). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and glutamine. This variant is present in population databases (rs542659326, ExAC 0.2%). This variant has not been reported in the literature in individuals affected with SKI-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV003375246 | SCV004094436 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-11-09 | criteria provided, single submitter | clinical testing | The c.242C>A (p.P81Q) alteration is located in exon 1 (coding exon 1) of the SKI gene. This alteration results from a C to A substitution at nucleotide position 242, causing the proline (P) at amino acid position 81 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |