ClinVar Miner

Submissions for variant NM_001032221.6(STXBP1):c.875G>A (p.Arg292His)

dbSNP: rs796053361
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189606 SCV000243251 pathogenic not provided 2021-05-11 criteria provided, single submitter clinical testing Published functional studies in C. elegans demonstrated that the transgenic R292H strain exhibited significantly reduced body bends on agar and showed significantly defective locomotion compared to worms expressing wild-type, and STXBP1 protein levels were reduced to 20-30% of wild-type, suggesting the variant results in STXBP1 protein instability (Zhu et al., 2020); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 19804848, 26795593, 30654231, 24781210, 26865513, 28628100, 29778030, 27779742, 29314583, 29896790, 29655203, 31171384, 31780880, 27905812, 26993267, 31105003, 32112430)
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000416099 SCV000677107 pathogenic Developmental and epileptic encephalopathy, 4 2017-11-09 criteria provided, single submitter research
Ambry Genetics RCV000623542 SCV000740849 pathogenic Inborn genetic diseases 2015-02-26 criteria provided, single submitter clinical testing
Invitae RCV000636416 SCV000757855 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-08-27 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 292 of the STXBP1 protein (p.Arg292His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with developmental/intellectual delay and seizures (PMID: 24781210, 26865513, 27779742). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 207424). 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. This variant disrupts the p.Arg292 amino acid residue in STXBP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26865513). 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.
Clinical Genetics and Genomics, Karolinska University Hospital RCV000189606 SCV001449840 likely pathogenic not provided 2016-09-19 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000416099 SCV002581746 pathogenic Developmental and epileptic encephalopathy, 4 2022-08-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000416099 SCV002805787 pathogenic Developmental and epileptic encephalopathy, 4 2021-08-20 criteria provided, single submitter clinical testing
GeneReviews RCV000416099 SCV000494038 not provided Developmental and epileptic encephalopathy, 4 no assertion provided literature only
GenomeConnect - Simons Searchlight RCV001265522 SCV001443666 pathogenic Infantile epilepsy syndrome 2018-11-21 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-11-21 and interpreted as Pathogenic. Variant was initially reported on 2018-06-15 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.
Pediatric Department, Xiangya Hospital, Central South University RCV000416099 SCV001961011 pathogenic Developmental and epileptic encephalopathy, 4 2020-01-09 no assertion criteria provided clinical testing

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