ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1264G>A (p.Ala422Thr) (rs760579911)

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
GeneDx RCV000196970 SCV000250693 uncertain significance not provided 2017-08-11 criteria provided, single submitter clinical testing p.Ala422Thr (GCA>ACA): c.1264 G>A in exon 4 of the SKI gene (NM_003036.3) Mutations in the SKI gene cause Shprintzen-Goldberg syndrome (SGS), a rare autosomal dominant disorder characterized by craniofacial, skeletal, neurological and cardiovascular anomalies. Cardiovascular anomalies of SGS include mitral valve prolapse and aortic root dilatation. Mutations in SKI usually occur de novo in the affected individual and are not inherited from an affected parent (Greally M, 2013; Carmignac et al., 2012, Doyle et al 2012). A variant of unknown significance has been identified in the SKI gene. The A422T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A422T variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A422T 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 conserved in mammals; however, T422 is present in several vertebrate species. Consequently, in silico analysis predicts this variant likely does not alter the protein structure/function. No missense mutations in nearby residues have been reported in association with Shprentzen-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
Ambry Genetics RCV000621546 SCV000739596 uncertain significance Cardiovascular phenotype 2017-04-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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.