Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189600 | SCV000243243 | pathogenic | not provided | 2022-01-07 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 23934111, 23708187, 26633542, 32581362, 32725632, 31175295, 33004838, 31130284) |
Invitae | RCV000796165 | SCV000935664 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 190 of the STXBP1 protein (p.Arg190Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with seizures (PMID: 26633542; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 207418). 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 expected to disrupt STXBP1 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg190 amino acid residue in STXBP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23708187, 23934111, 26514728, 26544041). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Genetics and Molecular Pathology, |
RCV002272167 | SCV002556455 | pathogenic | Developmental and epileptic encephalopathy, 4 | 2022-01-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345682 | SCV002648250 | uncertain significance | Inborn genetic diseases | 2020-01-22 | criteria provided, single submitter | clinical testing | The p.R190Q variant (also known as c.569G>A), located in coding exon 7 of the STXBP1 gene, results from a G to A substitution at nucleotide position 569. The arginine at codon 190 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a subject with epilepsy from a whole exome sequencing cohort (Retterer K et al. Genet. Med., 2016 07;18:696-704). Another alterations affecting the same amino acid, p.R190W (c.568C>T), has also been reported in association with epilepsy (Carvill GL et al. Nat. Genet., 2013 Jul;45:825-30). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Molecular Genetics Lab, |
RCV002272167 | SCV004697588 | likely pathogenic | Developmental and epileptic encephalopathy, 4 | criteria provided, single submitter | clinical testing | ||
Center for Genomic Medicine, |
RCV002272167 | SCV005016567 | pathogenic | Developmental and epileptic encephalopathy, 4 | 2024-03-14 | criteria provided, single submitter | clinical testing | |
NIHR Bioresource Rare Diseases, |
RCV001003592 | SCV001161986 | likely pathogenic | Autism; Neurodegeneration; Photosensitive tonic-clonic seizure; Intellectual disability, severe | no assertion criteria provided | research | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000189600 | SCV001799863 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000189600 | SCV001809746 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000189600 | SCV001930917 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |