ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.2128T>C (p.Trp710Arg)

gnomAD frequency: 0.00001  dbSNP: rs863223728
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196830 SCV000250696 uncertain significance not provided 2017-12-04 criteria provided, single submitter clinical testing p.Trp710Arg (TGG>CGG): c.2128 T>C in exon 7 of the SKI gene (NM_003036.3) A variant of unknown significance has been identified in the SKI gene. The W710R variant has not been published as a mutation or been reported as a benign polymorphism to our knowledge. The W710R variant was not observed in approximately 4600 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, the W710R 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. However, this substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported, indicating that 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 TAADV2-1
Baylor Genetics RCV001334106 SCV001526850 uncertain significance Shprintzen-Goldberg syndrome 2018-08-24 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002415843 SCV002728505 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-12-16 criteria provided, single submitter clinical testing The p.W710R variant (also known as c.2128T>C), located in coding exon 7 of the SKI gene, results from a T to C substitution at nucleotide position 2128. The tryptophan at codon 710 is replaced by arginine, an amino acid with dissimilar 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.

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