NM_001032221.6(STXBP1):c.1216C>T (p.Arg406Cys) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 25, 2020
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:: RCV000636419.12

Allele description [Variation Report for NM_001032221.6(STXBP1):c.1216C>T (p.Arg406Cys)]

NM_001032221.6(STXBP1):c.1216C>T (p.Arg406Cys)

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.1216C>T (p.Arg406Cys)

Other names:

p.R406C:CGC>TGC

HGVS:

NC_000009.12:g.127675909C>T
NG_016623.1:g.68703C>T
NM_001032221.6:c.1216C>TMANE SELECT
NM_001374306.2:c.1207C>T
NM_001374307.2:c.1174C>T
NM_001374308.2:c.1174C>T
NM_001374309.2:c.1174C>T
NM_001374310.2:c.1174C>T
NM_001374311.2:c.1174C>T
NM_001374312.2:c.1174C>T
NM_001374313.2:c.1216C>T
NM_001374314.1:c.1216C>T
NM_001374315.2:c.1108C>T
NM_003165.6:c.1216C>T
NP_001027392.1:p.Arg406Cys
NP_001361235.1:p.Arg403Cys
NP_001361236.1:p.Arg392Cys
NP_001361237.1:p.Arg392Cys
NP_001361238.1:p.Arg392Cys
NP_001361239.1:p.Arg392Cys
NP_001361240.1:p.Arg392Cys
NP_001361241.1:p.Arg392Cys
NP_001361242.1:p.Arg406Cys
NP_001361243.1:p.Arg406Cys
NP_001361244.1:p.Arg370Cys
NP_003156.1:p.Arg406Cys
NC_000009.11:g.130438188C>T
NM_001032221.3:c.1216C>T
NM_001032221.4:c.1216C>T
NM_001032221.6:c.1216C>T
NM_003165.2:c.1216C>T
NM_003165.3:c.1216C>T

Protein change:

R370C

Links:

dbSNP: rs796053367

NCBI 1000 Genomes Browser:

rs796053367

Molecular consequence:

NM_001032221.6:c.1216C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374306.2:c.1207C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374307.2:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374308.2:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374309.2:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374310.2:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374311.2:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374312.2:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374313.2:c.1216C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374314.1:c.1216C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374315.2:c.1108C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003165.6:c.1216C>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
SCV000757858	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 25, 2020)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 20887364, 21762454, 23934111, 26648591, 28387369, 28947817, 27171548, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000757858

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 25, 2020)

germline

clinical testing

PubMed (8)
[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

STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern.

Saitsu H, Kato M, Okada I, Orii KE, Higuchi T, Hoshino H, Kubota M, Arai H, Tagawa T, Kimura S, Sudo A, Miyama S, Takami Y, Watanabe T, Nishimura A, Nishiyama K, Miyake N, Wada T, Osaka H, Kondo N, Hayasaka K, Matsumoto N.

Epilepsia. 2010 Dec;51(12):2397-405. doi: 10.1111/j.1528-1167.2010.02728.x. Epub 2010 Sep 30.

PubMed [citation]

PMID:: 20887364

Mignot C, Moutard ML, Trouillard O, Gourfinkel-An I, Jacquette A, Arveiler B, Morice-Picard F, Lacombe D, Chiron C, Ville D, Charles P, LeGuern E, Depienne C, Héron D.

Epilepsia. 2011 Oct;52(10):1820-7. doi: 10.1111/j.1528-1167.2011.03163.x. Epub 2011 Jul 18.

PubMed [citation]

PMID:: 21762454

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000757858.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

A different missense substitution at this codon (p.Arg406His) has been determined to be pathogenic (PMID: 20887364, 21762454, 23934111). This suggests that the arginine residue is critical for STXBP1 protein function and that other missense substitutions at this position may also be pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported to be de novo in several individuals affected with early-onset epileptic encephalopathy (PMID: 26648591, 28387369) and several individuals affected with Rett-like syndrome (PMID: 28947817, 27171548). ClinVar contains an entry for this variant (Variation ID: 207431). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 406 of the STXBP1 protein (p.Arg406Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. 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: Oct 20, 2024

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