ClinVar Miner

Submissions for variant NM_001032221.6(STXBP1):c.874C>T (p.Arg292Cys)

dbSNP: rs786205598
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre RCV000171427 SCV000221625 likely pathogenic not provided criteria provided, single submitter research
GeneDx RCV000171427 SCV000243250 pathogenic not provided 2021-10-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 29655203, 29933521, 26865513, 26993267, 26112015, 29390993, 31487502, 32139178, 31105003, 31054490, 31031587, 24077912)
Fulgent Genetics, Fulgent Genetics RCV000515202 SCV000611324 pathogenic Developmental and epileptic encephalopathy, 4 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000700520 SCV000829278 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2021-08-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 292 of the STXBP1 protein (p.Arg292Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 26865513). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 191238). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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: 25356970, 26865513, 26993267). 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.
Mendelics RCV000515202 SCV001137906 pathogenic Developmental and epileptic encephalopathy, 4 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000171427 SCV001246232 pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV001266353 SCV001444527 pathogenic Inborn genetic diseases 2018-10-11 criteria provided, single submitter clinical testing
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris RCV001640264 SCV001519226 pathogenic Spastic ataxia 2021-01-04 criteria provided, single submitter research
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000515202 SCV002557107 pathogenic Developmental and epileptic encephalopathy, 4 2022-06-24 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with developmental and epileptic encephalopathy 4 (MIM#612164). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants. At least three other missense variants have been reported at this residue (ClinVar, DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least ten individuals, including de novo events and in patients with STXBP1 -encephalopathy (ClinVar, PMID: 26865513, 32643187). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan RCV003488419 SCV004232649 pathogenic West syndrome 2023-12-15 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000502114 SCV000597322 uncertain significance not specified 2013-06-06 flagged submission clinical testing
GenomeConnect, ClinGen RCV000509312 SCV000607363 not provided Early onset epileptic encephalopathy no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect - Simons Searchlight RCV001265420 SCV001443546 pathogenic Infantile epilepsy syndrome 2019-04-15 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2019-04-15 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.
Pediatric Department, Xiangya Hospital, Central South University RCV000515202 SCV001961012 pathogenic Developmental and epileptic encephalopathy, 4 2020-01-09 no assertion criteria provided clinical testing

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