ClinVar Miner

Submissions for variant NM_015559.3(SETBP1):c.2612T>C (p.Ile871Thr) (rs267607038)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000001086 SCV000194894 pathogenic Schinzel-Giedion syndrome 2013-11-27 criteria provided, single submitter clinical testing
GeneDx RCV000255245 SCV000322149 pathogenic not provided 2017-01-12 criteria provided, single submitter clinical testing The I871T variant in the SETBP1 gene has been reported previously in 5 unrelated individuals with Schinzel-Giedion syndrome and was confirmed to have occured de novo in all individuals for whom parental testing was available (Hoischen et al., 2010). The I871T variant was not observed in approximately 6,500 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 I871T variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same amino acid residue (I871S) has been reported in an individual with Schinzel-Giedion syndrome (Takeuchi et al., 2015). Additionally, missense variants in nearby residues (D868N, D868A, G870S, G870D, and G870C) have been reported in the Human Gene Mutation Database in association with Schinzel-Giedion syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret I871T as a pathogenic variant.
SIB Swiss Institute of Bioinformatics RCV000001086 SCV000803494 pathogenic Schinzel-Giedion syndrome 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Pathogenic, for Schinzel-Giedion midface retraction syndrome, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS2 => De novo (paternity and maternity confirmed) (PMID:20436468). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Recurrent mutation observed in multiple unrelated patients. (PMID:20436468,25028416). PS3-Moderate => PS3 downgraded in strength to Moderate (PMID:28346496).
Gharavi Laboratory,Columbia University RCV000255245 SCV000920674 uncertain significance not provided 2018-09-16 criteria provided, single submitter research
Cirak Lab,University Hospital Cologne RCV000855501 SCV000996631 pathogenic Fetal akinesia sequence; Arthrogryposis multiplex congenita 2019-06-28 criteria provided, single submitter research
OMIM RCV000001086 SCV000021236 pathogenic Schinzel-Giedion syndrome 2010-06-01 no assertion criteria provided literature only

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