ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1555C>T (p.Arg519Cys)

dbSNP: rs775800782
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197672 SCV000250682 uncertain significance not provided 2014-09-11 criteria provided, single submitter clinical testing p.Arg519Cys (CGT>TGT): c.1555 C>T in exon 5 of the SKI gene (NM_003036.3) A variant of unknown significance has been identified in the SKI gene. The R519C variant has not been published as a mutation or been reported as a benign polymorphism to our knowledge. The R519C 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. Although the R519C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties; this substitution occurs at a position that is not conserved across species. In addition, in silico analysis predicts this variant likely does not alter the protein structure/function. Lastly, no missense mutations in nearby residues have been reported in association with Shprintzen-Goldberg syndrome, suggesting this region of the protein may be tolerant of change.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD
Invitae RCV001301896 SCV001491081 uncertain significance Shprintzen-Goldberg syndrome 2021-02-08 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with SKI-related conditions. ClinVar contains an entry for this variant (Variation ID: 213696). This variant is present in population databases (rs775800782, ExAC 0.01%). This sequence change replaces arginine with cysteine at codon 519 of the SKI protein (p.Arg519Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine.
Revvity Omics, Revvity RCV001301896 SCV003823292 uncertain significance Shprintzen-Goldberg syndrome 2019-03-17 criteria provided, single submitter clinical testing

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