ClinVar Miner

Submissions for variant NM_001032221.6(STXBP1):c.704G>A (p.Arg235Gln)

dbSNP: rs794727970
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000180590 SCV000233061 pathogenic not provided 2015-05-26 criteria provided, single submitter clinical testing
GeneDx RCV000180590 SCV000243248 pathogenic not provided 2022-10-25 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 26865513, 25533962, 29056246, 28135719, 28191890, 29655203, 31474318, 34177756, 31175295, 31785789)
Genetic Services Laboratory, University of Chicago RCV000504117 SCV000597323 pathogenic Developmental and epileptic encephalopathy, 4 2017-05-15 criteria provided, single submitter clinical testing
Invitae RCV000796167 SCV000935666 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2022-11-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg235 amino acid residue in STXBP1. Other variant(s) that disrupt this residue have been observed in individuals with STXBP1-related conditions (PMID: 26865513, 29761117), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 199083). This missense change has been observed in individual(s) with STXBP1-related encephalopathy and/or intellectual disability (PMID: 25533962, 26865513). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 235 of the STXBP1 protein (p.Arg235Gln).
Institute of Human Genetics, University of Leipzig Medical Center RCV000504117 SCV001429025 pathogenic Developmental and epileptic encephalopathy, 4 2018-11-30 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000504117 SCV002021980 pathogenic Developmental and epileptic encephalopathy, 4 2019-08-01 criteria provided, single submitter clinical testing
Dobyns Lab, Seattle Children's Research Institute RCV000779652 SCV000916331 likely pathogenic Developmental and epileptic encephalopathy, 4; Cerebellar vermis hypoplasia 2019-02-18 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV001258012 SCV001434826 likely pathogenic Congenital cerebellar hypoplasia no assertion criteria provided research
GenomeConnect - Simons Searchlight RCV001265518 SCV001443662 likely pathogenic Infantile epilepsy syndrome 2018-11-30 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-11-30 and interpreted as Likely Pathogenic. Variant was initially reported by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.

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