Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000422578 | SCV000534849 | likely pathogenic | not provided | 2016-12-29 | criteria provided, single submitter | clinical testing | The E494V variant in the SATB2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E494V variant was not observed in approximately 6500 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 E494V 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 across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. As an alternate mechanism, multiple in silico algorithms predict that c.1481 A>T (aka E494V) might create a cryptic donor site in intron 10 which may supplant the natural donor site. However, in the absence of RNA/functional studies, the actual effect of c.1481 A>T in this individual is unknown. The E494V variant is a strong candidate for a pathogenic variant |
Labcorp Genetics |
RCV002298590 | SCV002593404 | uncertain significance | Chromosome 2q32-q33 deletion syndrome | 2022-09-13 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 391717). This variant has not been reported in the literature in individuals affected with SATB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 494 of the SATB2 protein (p.Glu494Val). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt SATB2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |