NM_001032221.6(STXBP1):c.416C>T (p.Pro139Leu) AND Developmental and epileptic encephalopathy, 4

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Jun 3, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000416131.15

Allele description [Variation Report for NM_001032221.6(STXBP1):c.416C>T (p.Pro139Leu)]

NM_001032221.6(STXBP1):c.416C>T (p.Pro139Leu)

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.416C>T (p.Pro139Leu)

Other names:

p.P139L:CCG>CTG

HGVS:

NC_000009.12:g.127661192C>T
NG_016623.1:g.53986C>T
NG_065187.1:g.71C>T
NM_001032221.6:c.416C>TMANE SELECT
NM_001374306.2:c.407C>T
NM_001374307.2:c.374C>T
NM_001374308.2:c.374C>T
NM_001374309.2:c.374C>T
NM_001374310.2:c.374C>T
NM_001374311.2:c.374C>T
NM_001374312.2:c.374C>T
NM_001374313.2:c.416C>T
NM_001374314.1:c.416C>T
NM_001374315.2:c.416C>T
NM_003165.6:c.416C>T
NP_001027392.1:p.Pro139Leu
NP_001361235.1:p.Pro136Leu
NP_001361236.1:p.Pro125Leu
NP_001361237.1:p.Pro125Leu
NP_001361238.1:p.Pro125Leu
NP_001361239.1:p.Pro125Leu
NP_001361240.1:p.Pro125Leu
NP_001361241.1:p.Pro125Leu
NP_001361242.1:p.Pro139Leu
NP_001361243.1:p.Pro139Leu
NP_001361244.1:p.Pro139Leu
NP_003156.1:p.Pro139Leu
NC_000009.11:g.130423471C>T
NM_003165.3:c.416C>T

Protein change:

P125L

Links:

dbSNP: rs796053353

NCBI 1000 Genomes Browser:

rs796053353

Molecular consequence:

NM_001032221.6:c.416C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374306.2:c.407C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374307.2:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374308.2:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374309.2:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374310.2:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374311.2:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374312.2:c.374C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374313.2:c.416C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374314.1:c.416C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374315.2:c.416C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003165.6:c.416C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Developmental and epileptic encephalopathy, 4 (DEE4)
Synonyms:: Early infantile epileptic encephalopathy 4; STXBP1-Related Epileptic Encephalopathy
Identifiers:: MONDO: MONDO:0012812; MedGen: C2677326; Orphanet: 1934; Orphanet: 33069; OMIM: 612164

Recent activity

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Profile neighbors for GEO Profiles (Select 20804839) (200)
GEO Profiles
Metagenome or environmental sample from Euryarchaeota archaeon RBG_13_61_15
Metagenome or environmental sample from Euryarchaeota archaeon RBG_13_61_15

biosample
BioSample links for Nucleotide (Select 1085051345) (1)
BioSample
Danio rerio chromosome 7 genomic contig ALT_CTG7_1_6, GRCz11 reference assembly ...
Danio rerio chromosome 7 genomic contig ALT_CTG7_1_6, GRCz11 reference assembly alternate locus group ALT_DRER_TU_1
gi|1193823565|gnl|ASM:GCA_002119155 T_CTG7_1_6|gb|KZ115213.1|

Nucleotide
magnesium transporter NIPA2 isoform X2 [Homo sapiens]
magnesium transporter NIPA2 isoform X2 [Homo sapiens]
gi|2462546208|ref|XP_054234939.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000494035	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 24189369, 25418441
SCV000680006	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 6, 2016)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000693796	NeuroMeGen, Hospital Clinico Santiago de Compostela	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 1, 2018)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001429392	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 3, 2019)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001760226	Genomics England Pilot Project, Genomics England	no assertion criteria provided (ACGS Guidelines, 2016)	Pathogenic	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only
not provided	de novo	yes	3	1	not provided	4	not provided	clinical testing

Citations

PubMed

Early epileptic encephalopathies associated with STXBP1 mutations: Could we better delineate the phenotype?

Barcia G, Chemaly N, Gobin S, Milh M, Van Bogaert P, Barnerias C, Kaminska A, Dulac O, Desguerre I, Cormier V, Boddaert N, Nabbout R.

Eur J Med Genet. 2014 Jan;57(1):15-20. doi: 10.1016/j.ejmg.2013.10.006. Epub 2013 Nov 1.

PubMed [citation]

PMID:: 24189369

A novel de novo STXBP1 mutation is associated with mitochondrial complex I deficiency and late-onset juvenile-onset parkinsonism.

Keogh MJ, Daud D, Pyle A, Duff J, Griffin H, He L, Alston CL, Steele H, Taggart S, Basu AP, Taylor RW, Horvath R, Ramesh V, Chinnery PF.

Neurogenetics. 2015 Jan;16(1):65-7. doi: 10.1007/s10048-014-0431-z. Epub 2014 Nov 25.

PubMed [citation]

PMID:: 25418441
PMCID:: PMC6600868

See all PubMed Citations (3)

Details of each submission

From GeneReviews, SCV000494035.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

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

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV000680006.1

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

Description

A heterozygous nonsense variant was identified, NM_003165.3(STXBP1):c.416C>T in exon 6 of the STXBP1 gene (chr9:130423471). This substitution is predicted to create a change of a proline to a leucine at amino acid position 139, NP_003156.1(STXBP1):p.(Pro139Leu). The proline at this position has high conservation and is located in a SEC1-like domain. Grantham assessment is likely pathogenic for this variant due to conservation. In silico software predicts this variant to be disease causing. This variant has not been previously observed in our patient cohort and has not been observed in population databases. It has been previously reported in patients with epileptic encephalopathies (Barcia G. et al. 2014, Eur J Med Genet; Keogh MJ. et al, 2016, Neurogenetics, ClinVar). Parental testing confirmed de novo status. Based on current information this variant has been classified as PATHOGENIC.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	3	Blood	not provided		1	not provided	1	not provided

From NeuroMeGen, Hospital Clinico Santiago de Compostela, SCV000693796.1

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

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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001429392.1

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

Description

This variant was identified as de novo (maternity and paternity confirmed).

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

From Genomics England Pilot Project, Genomics England, SCV001760226.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

Last Updated: May 12, 2024

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