Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004240825 | SCV003753645 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-05-18 | criteria provided, single submitter | clinical testing | The c.1589C>T (p.A530V) alteration is located in exon 5 (coding exon 5) of the SKI gene. This alteration results from a C to T substitution at nucleotide position 1589, causing the alanine (A) at amino acid position 530 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Invitae | RCV003631287 | SCV004559745 | uncertain significance | Shprintzen-Goldberg syndrome | 2023-12-20 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 530 of the SKI protein (p.Ala530Val). This variant is present in population databases (no rsID available, gnomAD 0.001%). 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: 2402191). 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 not expected to disrupt SKI protein function with a negative predictive value of 95%. 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. |