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

dbSNP: rs794727970

Total submissions: 9

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.