U.S. flag

An official website of the United States government

NM_001040142.2(SCN2A):c.3631G>A (p.Glu1211Lys) AND Developmental and epileptic encephalopathy, 11

Germline classification:
Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:
Sep 28, 2022
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:
RCV000022767.31

Allele description [Variation Report for NM_001040142.2(SCN2A):c.3631G>A (p.Glu1211Lys)]

NM_001040142.2(SCN2A):c.3631G>A (p.Glu1211Lys)

Gene:
SCN2A:sodium voltage-gated channel alpha subunit 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001040142.2(SCN2A):c.3631G>A (p.Glu1211Lys)
Other names:
p.E1211K:GAA>AAA
HGVS:
  • NC_000002.12:g.165367327G>A
  • NG_008143.1:g.132926G>A
  • NM_001040142.2:c.3631G>AMANE SELECT
  • NM_001040143.2:c.3631G>A
  • NM_001371246.1:c.3631G>A
  • NM_001371247.1:c.3631G>A
  • NM_021007.3:c.3631G>A
  • NP_001035232.1:p.Glu1211Lys
  • NP_001035233.1:p.Glu1211Lys
  • NP_001358175.1:p.Glu1211Lys
  • NP_001358176.1:p.Glu1211Lys
  • NP_066287.2:p.Glu1211Lys
  • NP_066287.2:p.Glu1211Lys
  • NC_000002.11:g.166223837G>A
  • NM_001040142.1:c.3631G>A
  • NM_001040143.2:c.3631G>A
  • NM_021007.2:c.3631G>A
  • Q99250:p.Glu1211Lys
Protein change:
E1211K; GLU1211LYS
Links:
UniProtKB: Q99250#VAR_065180; OMIM: 182390.0009; dbSNP: rs387906684
NCBI 1000 Genomes Browser:
rs387906684
Molecular consequence:
  • NM_001040142.2:c.3631G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001040143.2:c.3631G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371246.1:c.3631G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371247.1:c.3631G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021007.3:c.3631G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
  • Mild-moderate slowing of recovery from fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0056]
  • Overall mixed or unclear functional effect not able to be clearly categorized as Gain- or Loss-of-Function [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0145]
  • Severe hyperpolarizing shift of voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0031]
  • Severe hyperpolarizing shift of voltage dependence of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0069]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 11 (DEE11)
Synonyms:
Early infantile epileptic encephalopathy 11
Identifiers:
MONDO: MONDO:0013388; MedGen: C3150987; Orphanet: 1934; OMIM: 613721

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000044056OMIM
no assertion criteria provided
Pathogenic
(Sep 29, 2009)
germlineliterature only

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

SCV000255458UCLA Clinical Genomics Center, UCLA - CES
criteria provided, single submitter

(Lee et al. (JAMA. 2014))
Likely pathogenic
(Jul 16, 2013)
de novoclinical testing

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

SCV004013955Laboratory of Medical Genetics, National & Kapodistrian University of Athens
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Sep 28, 2022)
germlineclinical testing

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

SCV004048337Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenicgermlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies.

Ogiwara I, Ito K, Sawaishi Y, Osaka H, Mazaki E, Inoue I, Montal M, Hashikawa T, Shike T, Fujiwara T, Inoue Y, Kaneda M, Yamakawa K.

Neurology. 2009 Sep 29;73(13):1046-53. doi: 10.1212/WNL.0b013e3181b9cebc.

PubMed [citation]
PMID:
19786696
PMCID:
PMC2754324

Clinical exome sequencing for genetic identification of rare Mendelian disorders.

Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, Das K, Toy T, Harry B, Yourshaw M, Fox M, Fogel BL, Martinez-Agosto JA, Wong DA, Chang VY, Shieh PB, Palmer CG, Dipple KM, Grody WW, Vilain E, Nelson SF.

JAMA. 2014 Nov 12;312(18):1880-7. doi: 10.1001/jama.2014.14604.

PubMed [citation]
PMID:
25326637
PMCID:
PMC4278636
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000044056.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 22-year-old man with developmental and epileptic encephalopathy-11 (DEE11; 613721), Ogiwara et al. (2009) identified a de novo heterozygous c.3631G-A transition in the SCN2A gene, resulting in a glu1211-to-lys (E1211K) substitution. The patient had onset of infantile spasms at age 11 months, which evolved to frequent occurrence of refractory tonic-clonic seizures at age 2 to 3 years. He also showed marked developmental delay and severe intellectual disability in infancy and childhood. Febrile seizures occurred after age 10 years. After an episode of status epilepticus at age 17 years, he became quadriplegic and speechless. In vitro electrophysiologic studies indicated that the E1211K mutant channel had properties compatible with both augmented and reduced channel activities. There was an 18-mV hyperpolarizing shift in the voltage dependence of activation, as well as a 22-mV hyperpolarizing shift in the voltage dependence of steady-state inactivation and slowed recovery from inactivation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From UCLA Clinical Genomics Center, UCLA - CES, SCV000255458.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV004013955.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

PM2, PP3, PP5

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004048337.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The amino acid Glu at position 1211 is changed to a Lys changing protein sequence and it might alter its composition and physico-chemical properties. This variant has been reported in individuals with clinical features of early infantile epileptic encephalopathy (Ogiwara et al, 2009, Lee et al, 2014). Experimental studies have shown that this missense change significantly changed the functional property of the sodium channels leading to both augmented and reduced channel activities by electrophysiological analyses in the cells (Ogiwara et al, 2009). The p.Glu1211Lys variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Glu1211Lys in SCN2A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 30, 2024