ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1330G>A (p.Glu444Lys)

gnomAD frequency: 0.00001  dbSNP: rs747693633
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038944 SCV001202446 uncertain significance Shprintzen-Goldberg syndrome 2023-11-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 444 of the SKI protein (p.Glu444Lys). This variant is present in population databases (rs747693633, gnomAD 0.007%). 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: 837577). 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. 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 RCV003363056 SCV004070644 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-06-17 criteria provided, single submitter clinical testing The p.E444K variant (also known as c.1330G>A), located in coding exon 4 of the SKI gene, results from a G to A substitution at nucleotide position 1330. The glutamic acid at codon 444 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.