Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000799049 | SCV000938696 | uncertain significance | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2544 of the SZT2 protein (p.Arg2544His). This variant is present in population databases (rs757425191, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SZT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 645034). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SZT2 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. |
Ce |
RCV000799049 | SCV001247450 | uncertain significance | not provided | 2019-07-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000799049 | SCV002012553 | uncertain significance | not provided | 2021-10-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002388465 | SCV002672801 | uncertain significance | Inborn genetic diseases | 2017-07-18 | criteria provided, single submitter | clinical testing | The p.R2544H variant (also known as c.7631G>A), located in coding exon 55 of the SZT2 gene, results from a G to A substitution at nucleotide position 7631. The arginine at codon 2544 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV003457806 | SCV004181518 | uncertain significance | Developmental and epileptic encephalopathy, 18 | 2023-04-11 | criteria provided, single submitter | clinical testing |