ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.2056G>A (p.Ala686Thr) (rs756553942)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195941 SCV000250695 uncertain significance not provided 2014-12-01 criteria provided, single submitter clinical testing p.Ala686Thr (GCC>ACC): c.2056 G>A in exon 7 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 A686T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A686T variant was not observed in approximately 5,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A686T 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. Additionally, this substitution occurs at a position that is conserved among mammals. However, 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 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,TAADV2-1

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