NM_001032221.6(STXBP1):c.847G>A (p.Glu283Lys) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 12, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000525775.9

Allele description [Variation Report for NM_001032221.6(STXBP1):c.847G>A (p.Glu283Lys)]

NM_001032221.6(STXBP1):c.847G>A (p.Glu283Lys)

Gene:

STXBP1:syntaxin binding protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001032221.6(STXBP1):c.847G>A (p.Glu283Lys)

HGVS:

NC_000009.12:g.127668132G>A
NG_016623.1:g.60926G>A
NM_001032221.6:c.847G>AMANE SELECT
NM_001374306.2:c.838G>A
NM_001374307.2:c.805G>A
NM_001374308.2:c.805G>A
NM_001374309.2:c.805G>A
NM_001374310.2:c.805G>A
NM_001374311.2:c.805G>A
NM_001374312.2:c.805G>A
NM_001374313.2:c.847G>A
NM_001374314.1:c.847G>A
NM_001374315.2:c.795-1766G>A
NM_003165.6:c.847G>A
NP_001027392.1:p.Glu283Lys
NP_001361235.1:p.Glu280Lys
NP_001361236.1:p.Glu269Lys
NP_001361237.1:p.Glu269Lys
NP_001361238.1:p.Glu269Lys
NP_001361239.1:p.Glu269Lys
NP_001361240.1:p.Glu269Lys
NP_001361241.1:p.Glu269Lys
NP_001361242.1:p.Glu283Lys
NP_001361243.1:p.Glu283Lys
NP_003156.1:p.Glu283Lys
NC_000009.11:g.130430411G>A
NM_003165.3:c.847G>A
P61764:p.Glu283Lys

Protein change:

E269K; GLU283LYS

Links:

UniProtKB: P61764#VAR_071814; OMIM: 602926.0008; dbSNP: rs587777310

NCBI 1000 Genomes Browser:

rs587777310

Molecular consequence:

NM_001374315.2:c.795-1766G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001032221.6:c.847G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374306.2:c.838G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374307.2:c.805G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374308.2:c.805G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374309.2:c.805G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374310.2:c.805G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374311.2:c.805G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374312.2:c.805G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374313.2:c.847G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374314.1:c.847G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003165.6:c.847G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:: Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000633905	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 12, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24623842, 26865513, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000633905

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 12, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

GABRA1 and STXBP1: novel genetic causes of Dravet syndrome.

Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Møller RS, Hjalgrim H, Cook J, Geraghty E, O'Roak BJ, Petrou S, Clarke A, Gill D, Sadleir LG, Muhle H, von Spiczak S, Nikanorova M, Hodgson BL, Gazina EV, Suls A, Shendure J, Dibbens LM, De Jonghe P, et al.

Neurology. 2014 Apr 8;82(14):1245-53. doi: 10.1212/WNL.0000000000000291. Epub 2014 Mar 12.

PubMed [citation]

PMID:: 24623842
PMCID:: PMC4001207

STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.

Stamberger H, Nikanorova M, Willemsen MH, Accorsi P, Angriman M, Baier H, Benkel-Herrenbrueck I, Benoit V, Budetta M, Caliebe A, Cantalupo G, Capovilla G, Casara G, Courage C, Deprez M, Destrée A, Dilena R, Erasmus CE, Fannemel M, Fjær R, Giordano L, Helbig KL, et al.

Neurology. 2016 Mar 8;86(10):954-62. doi: 10.1212/WNL.0000000000002457. Epub 2016 Feb 10. Review.

PubMed [citation]

PMID:: 26865513

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000633905.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 283 of the STXBP1 protein (p.Glu283Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Dravet syndrome and intractable epilepsy (PMID: 24623842, 26865513; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 127076). 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%. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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