ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1480T>A (p.Ser494Thr) (rs781304969)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414146 SCV000492366 uncertain significance not specified 2016-12-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SKI gene. The S494T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S494T variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, although this substitution occurs at a position that is conserved in mammals, S494T is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV000460773 SCV000550381 uncertain significance Shprintzen-Goldberg syndrome 2016-08-18 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 494 of the SKI protein (p.Ser494Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SKI-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000621347 SCV000739619 uncertain significance Cardiovascular phenotype 2016-09-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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