NM_001165963.4(SCN1A):c.626T>G (p.Leu209Arg) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 7, 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:: RCV003754372.2

Allele description [Variation Report for NM_001165963.4(SCN1A):c.626T>G (p.Leu209Arg)]

NM_001165963.4(SCN1A):c.626T>G (p.Leu209Arg)

Gene:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.626T>G (p.Leu209Arg)

HGVS:

NC_000002.12:g.166052920A>C
NG_011906.1:g.25720T>G
NM_001165963.4:c.626T>GMANE SELECT
NM_001165964.3:c.626T>G
NM_001202435.3:c.626T>G
NM_001353948.2:c.626T>G
NM_001353949.2:c.626T>G
NM_001353950.2:c.626T>G
NM_001353951.2:c.626T>G
NM_001353952.2:c.626T>G
NM_001353954.2:c.626T>G
NM_001353955.2:c.626T>G
NM_001353957.2:c.626T>G
NM_001353958.2:c.626T>G
NM_001353960.2:c.626T>G
NM_001353961.2:c.-1800T>G
NM_006920.6:c.626T>G
NP_001159435.1:p.Leu209Arg
NP_001159436.1:p.Leu209Arg
NP_001189364.1:p.Leu209Arg
NP_001340877.1:p.Leu209Arg
NP_001340878.1:p.Leu209Arg
NP_001340879.1:p.Leu209Arg
NP_001340880.1:p.Leu209Arg
NP_001340881.1:p.Leu209Arg
NP_001340883.1:p.Leu209Arg
NP_001340884.1:p.Leu209Arg
NP_001340886.1:p.Leu209Arg
NP_001340887.1:p.Leu209Arg
NP_001340889.1:p.Leu209Arg
NP_008851.3:p.Leu209Arg
NP_008851.3:p.Leu209Arg
LRG_8t1:c.626T>G
LRG_8:g.25720T>G
LRG_8p1:p.Leu209Arg
NC_000002.11:g.166909430A>C
NM_006920.4:c.626T>G
NR_148667.2:n.1012T>G

Protein change:

L209R

Molecular consequence:

NM_001353961.2:c.-1800T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.626T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.1012T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004427240	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31031587, 31618474, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004427240

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 7, 2023)

germline

clinical testing

PubMed (3)
[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

Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes.

Xiong J, Chen S, Pang N, Deng X, Yang L, He F, Wu L, Chen C, Yin F, Peng J.

Front Neurosci. 2019;13:349. doi: 10.3389/fnins.2019.00349.

PubMed [citation]

PMID:: 31031587
PMCID:: PMC6470315

The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures.

Burgess R, Wang S, McTague A, Boysen KE, Yang X, Zeng Q, Myers KA, Rochtus A, Trivisano M, Gill D; EIMFS Consortium., Sadleir LG, Specchio N, Guerrini R, Marini C, Zhang YH, Mefford HC, Kurian MA, Poduri AH, Scheffer IE.

Ann Neurol. 2019 Dec;86(6):821-831. doi: 10.1002/ana.25619. Erratum in: Ann Neurol. 2020 Apr;87(4):658. doi: 10.1002/ana.25703.

PubMed [citation]

PMID:: 31618474
PMCID:: PMC7423163

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004427240.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant disrupts the p.Leu209 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31031587, 31618474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 SCN1A protein function. This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 209 of the SCN1A protein (p.Leu209Arg).

#	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