NM_001032221.6(STXBP1):c.1697T>C (p.Leu566Pro) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 30, 2022
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:: RCV003753221.2

Allele description [Variation Report for NM_001032221.6(STXBP1):c.1697T>C (p.Leu566Pro)]

NM_001032221.6(STXBP1):c.1697T>C (p.Leu566Pro)

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.1697T>C (p.Leu566Pro)

HGVS:

NC_000009.12:g.127682555T>C
NG_016623.1:g.75349T>C
NM_001032221.6:c.1697T>CMANE SELECT
NM_001374306.2:c.1688T>C
NM_001374307.2:c.1655T>C
NM_001374308.2:c.1655T>C
NM_001374309.2:c.1655T>C
NM_001374310.2:c.1655T>C
NM_001374311.2:c.1655T>C
NM_001374312.2:c.1655T>C
NM_001374313.2:c.1697T>C
NM_001374314.1:c.1697T>C
NM_001374315.2:c.1589T>C
NM_003165.6:c.1697T>C
NP_001027392.1:p.Leu566Pro
NP_001361235.1:p.Leu563Pro
NP_001361236.1:p.Leu552Pro
NP_001361237.1:p.Leu552Pro
NP_001361238.1:p.Leu552Pro
NP_001361239.1:p.Leu552Pro
NP_001361240.1:p.Leu552Pro
NP_001361241.1:p.Leu552Pro
NP_001361242.1:p.Leu566Pro
NP_001361243.1:p.Leu566Pro
NP_001361244.1:p.Leu530Pro
NP_003156.1:p.Leu566Pro
NC_000009.11:g.130444834T>C

Protein change:

L530P

Links:

dbSNP: rs2131536431

NCBI 1000 Genomes Browser:

rs2131536431

Molecular consequence:

NM_001032221.6:c.1697T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374306.2:c.1688T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374307.2:c.1655T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374308.2:c.1655T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374309.2:c.1655T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374310.2:c.1655T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374311.2:c.1655T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374312.2:c.1655T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374313.2:c.1697T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374314.1:c.1697T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374315.2:c.1589T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003165.6:c.1697T>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004376772	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 30, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32005694, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004376772

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 30, 2022)

germline

clinical testing

PubMed (2)
[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

Clinical exome sequencing as the first-tier test for diagnosing developmental disorders covering both CNV and SNV: a Chinese cohort.

Dong X, Liu B, Yang L, Wang H, Wu B, Liu R, Chen H, Chen X, Yu S, Chen B, Wang S, Xu X, Zhou W, Lu Y.

J Med Genet. 2020 Aug;57(8):558-566. doi: 10.1136/jmedgenet-2019-106377. Epub 2020 Jan 31.

PubMed [citation]

PMID:: 32005694
PMCID:: PMC7418612

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, SCV004376772.1

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

Description

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. 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. ClinVar contains an entry for this variant (Variation ID: 1691005). This missense change has been observed in individual(s) with isolated developmental delay (PMID: 32005694). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 566 of the STXBP1 protein (p.Leu566Pro).

#	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

ClinVar

Relating variation to medicine