NM_001032221.6(STXBP1):c.746T>C (p.Phe249Ser) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 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:: RCV002959141.3

Allele description [Variation Report for NM_001032221.6(STXBP1):c.746T>C (p.Phe249Ser)]

NM_001032221.6(STXBP1):c.746T>C (p.Phe249Ser)

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.746T>C (p.Phe249Ser)

HGVS:

NC_000009.12:g.127666248T>C
NG_016623.1:g.59042T>C
NG_016623.2:g.59338T>C
NM_001032221.6:c.746T>CMANE SELECT
NM_001374306.2:c.737T>C
NM_001374307.2:c.704T>C
NM_001374308.2:c.704T>C
NM_001374309.2:c.704T>C
NM_001374310.2:c.704T>C
NM_001374311.2:c.704T>C
NM_001374312.2:c.704T>C
NM_001374313.2:c.746T>C
NM_001374314.1:c.746T>C
NM_001374315.2:c.746T>C
NM_003165.6:c.746T>C
NP_001027392.1:p.Phe249Ser
NP_001361235.1:p.Phe246Ser
NP_001361236.1:p.Phe235Ser
NP_001361237.1:p.Phe235Ser
NP_001361238.1:p.Phe235Ser
NP_001361239.1:p.Phe235Ser
NP_001361240.1:p.Phe235Ser
NP_001361241.1:p.Phe235Ser
NP_001361242.1:p.Phe249Ser
NP_001361243.1:p.Phe249Ser
NP_001361244.1:p.Phe249Ser
NP_003156.1:p.Phe249Ser
NC_000009.11:g.130428527T>C

Protein change:

F235S

Molecular consequence:

NM_001032221.6:c.746T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374306.2:c.737T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374307.2:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374308.2:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374309.2:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374310.2:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374311.2:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374312.2:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374313.2:c.746T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374314.1:c.746T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374315.2:c.746T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003165.6:c.746T>C - 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
SCV003282411	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	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

SCV003282411

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

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, SCV003282411.2

#	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 phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 249 of the STXBP1 protein (p.Phe249Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STXBP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2070629). 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. 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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