ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1706T>C (p.Met569Thr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002398806 SCV002712885 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-03-17 criteria provided, single submitter clinical testing The p.M569T variant (also known as c.1706T>C), located in coding exon 5 of the SKI gene, results from a T to C substitution at nucleotide position 1706. The methionine at codon 569 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003097145 SCV003262993 uncertain significance Shprintzen-Goldberg syndrome 2024-09-29 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 569 of the SKI protein (p.Met569Thr). This variant is present in population databases (rs539988362, gnomAD 0.002%). 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: 1778462). Invitae Evidence 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 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.

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