NM_001032221.6(STXBP1):c.1651C>T (p.Arg551Cys) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 10, 2023
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:: RCV001071757.13

Allele description [Variation Report for NM_001032221.6(STXBP1):c.1651C>T (p.Arg551Cys)]

NM_001032221.6(STXBP1):c.1651C>T (p.Arg551Cys)

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.1651C>T (p.Arg551Cys)

Other names:

p.R551C:CGC>TGC

HGVS:

NC_000009.12:g.127682509C>T
NG_016623.1:g.75303C>T
NM_001032221.6:c.1651C>TMANE SELECT
NM_001374306.2:c.1642C>T
NM_001374307.2:c.1609C>T
NM_001374308.2:c.1609C>T
NM_001374309.2:c.1609C>T
NM_001374310.2:c.1609C>T
NM_001374311.2:c.1609C>T
NM_001374312.2:c.1609C>T
NM_001374313.2:c.1651C>T
NM_001374314.1:c.1651C>T
NM_001374315.2:c.1543C>T
NM_003165.6:c.1651C>T
NP_001027392.1:p.Arg551Cys
NP_001361235.1:p.Arg548Cys
NP_001361236.1:p.Arg537Cys
NP_001361237.1:p.Arg537Cys
NP_001361238.1:p.Arg537Cys
NP_001361239.1:p.Arg537Cys
NP_001361240.1:p.Arg537Cys
NP_001361241.1:p.Arg537Cys
NP_001361242.1:p.Arg551Cys
NP_001361243.1:p.Arg551Cys
NP_001361244.1:p.Arg515Cys
NP_003156.1:p.Arg551Cys
NC_000009.11:g.130444788C>T
NM_003165.3:c.1651C>T

Protein change:

R515C

Links:

dbSNP: rs796053373

NCBI 1000 Genomes Browser:

rs796053373

Molecular consequence:

NM_001032221.6:c.1651C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374306.2:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374307.2:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374308.2:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374309.2:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374310.2:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374311.2:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374312.2:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374313.2:c.1651C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374314.1:c.1651C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374315.2:c.1543C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003165.6:c.1651C>T - 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
SCV001237078	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23409955, 26865513, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001237078

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 10, 2023)

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

Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers.

Weckhuysen S, Holmgren P, Hendrickx R, Jansen AC, Hasaerts D, Dielman C, de Bellescize J, Boutry-Kryza N, Lesca G, Von Spiczak S, Helbig I, Gill D, Yendle S, Møller RS, Klitten L, Korff C, Godfraind C, Van Rijckevorsel K, De Jonghe P, Hjalgrim H, Scheffer IE, Suls A.

Epilepsia. 2013 May;54(5):e74-80. doi: 10.1111/epi.12124. Epub 2013 Feb 14.

PubMed [citation]

PMID:: 23409955

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 Invitae, SCV001237078.5

#	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 arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 551 of the STXBP1 protein (p.Arg551Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with early-onset epileptic encephalopathy (PMID: 23409955, 26865513). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 207440). 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%. This variant disrupts the p.Arg551 amino acid residue in STXBP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26865513; Invitae). 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.

#	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: May 19, 2024

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