NM_001032221.6(STXBP1):c.1657G>A (p.Ala553Thr) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 29, 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:: RCV003753892.2

Allele description [Variation Report for NM_001032221.6(STXBP1):c.1657G>A (p.Ala553Thr)]

NM_001032221.6(STXBP1):c.1657G>A (p.Ala553Thr)

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.1657G>A (p.Ala553Thr)

HGVS:

NC_000009.12:g.127682515G>A
NG_016623.1:g.75309G>A
NG_016623.2:g.75605G>A
NM_001032221.6:c.1657G>AMANE SELECT
NM_001374306.2:c.1648G>A
NM_001374307.2:c.1615G>A
NM_001374308.2:c.1615G>A
NM_001374309.2:c.1615G>A
NM_001374310.2:c.1615G>A
NM_001374311.2:c.1615G>A
NM_001374312.2:c.1615G>A
NM_001374313.2:c.1657G>A
NM_001374314.1:c.1657G>A
NM_001374315.2:c.1549G>A
NM_003165.6:c.1657G>A
NP_001027392.1:p.Ala553Thr
NP_001361235.1:p.Ala550Thr
NP_001361236.1:p.Ala539Thr
NP_001361237.1:p.Ala539Thr
NP_001361238.1:p.Ala539Thr
NP_001361239.1:p.Ala539Thr
NP_001361240.1:p.Ala539Thr
NP_001361241.1:p.Ala539Thr
NP_001361242.1:p.Ala553Thr
NP_001361243.1:p.Ala553Thr
NP_001361244.1:p.Ala517Thr
NP_003156.1:p.Ala553Thr
NC_000009.11:g.130444794G>A

Protein change:

A517T

Molecular consequence:

NM_001032221.6:c.1657G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374306.2:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374307.2:c.1615G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374308.2:c.1615G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374309.2:c.1615G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374310.2:c.1615G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374311.2:c.1615G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374312.2:c.1615G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374313.2:c.1657G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374314.1:c.1657G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374315.2:c.1549G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003165.6:c.1657G>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
SCV004392613	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004392613

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 29, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004392613.1

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 553 of the STXBP1 protein (p.Ala553Thr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with STXBP1-related conditions. 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%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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