ClinVar Miner

Submissions for variant NM_001172509.2(SATB2):c.1165C>T (p.Arg389Cys) (rs1057521083)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430827 SCV000520981 pathogenic not provided 2018-12-13 criteria provided, single submitter clinical testing The R389C variant in the SATB2 gene has been reported previously in an individual with cleft palate, congenital myopia, global developmental delay, and micrognathia, as well as in the de novo state in an individual with intellectual disability, developmental delay, behavioral problems, and Pierre-Robin sequence (Trakadis et al., 2014; Bengani et al., 2017). The R389C variant has been reported in the de novo state in three individuals with SATB2-related disorders (Zarate et al., 2018). A transfection study to determine the effect of R389C on subcellular localization showed a more diffuse pattern compared to wild-type (Bengani et al., 2017). The R389C variant is not observed in large population cohorts (Lek et al., 2016). The R389C 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret R389C as a pathogenic variant.
Ambry Genetics RCV000623230 SCV000742208 likely pathogenic Inborn genetic diseases 2017-02-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000656508 SCV000890009 pathogenic Chromosome 2q32-q33 deletion syndrome 2017-03-16 criteria provided, single submitter clinical testing
Invitae RCV000656508 SCV000932629 pathogenic Chromosome 2q32-q33 deletion syndrome 2018-09-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 389 of the SATB2 protein (p.Arg389Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with SATB2-related disease (PMID: 28151491). ClinVar contains an entry for this variant (Variation ID: 381575). Experimental studies have shown that this missense change alters sub-cellular localization and chromatin association ability of the protein (PMID: 28151491). This variant disrupts the p.Arg389 amino acid residue in SATB2. Other variant that disrupts this residue has been observed in affected individuals (PMID: 28151491), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000656508 SCV000778505 pathogenic Chromosome 2q32-q33 deletion syndrome 2018-06-15 no assertion criteria provided literature only
GeneReviews RCV000656508 SCV000837669 pathogenic Chromosome 2q32-q33 deletion syndrome 2017-06-02 no assertion criteria provided literature only

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