NM_001165963.4(SCN1A):c.3734G>A (p.Arg1245Gln) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 16, 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:: RCV000636387.6

Allele description [Variation Report for NM_001165963.4(SCN1A):c.3734G>A (p.Arg1245Gln)]

NM_001165963.4(SCN1A):c.3734G>A (p.Arg1245Gln)

Genes:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.3734G>A (p.Arg1245Gln)

Other names:

p.R1245Q:CGA>CAA

HGVS:

NC_000002.12:g.166012254C>T
NG_011906.1:g.66386G>A
NM_001165963.4:c.3734G>AMANE SELECT
NM_001165964.3:c.3650G>A
NM_001202435.3:c.3734G>A
NM_001353948.2:c.3734G>A
NM_001353949.2:c.3701G>A
NM_001353950.2:c.3701G>A
NM_001353951.2:c.3701G>A
NM_001353952.2:c.3701G>A
NM_001353954.2:c.3698G>A
NM_001353955.2:c.3698G>A
NM_001353957.2:c.3650G>A
NM_001353958.2:c.3650G>A
NM_001353960.2:c.3647G>A
NM_001353961.2:c.1292G>A
NM_006920.6:c.3701G>A
NP_001159435.1:p.Arg1245Gln
NP_001159436.1:p.Arg1217Gln
NP_001189364.1:p.Arg1245Gln
NP_001340877.1:p.Arg1245Gln
NP_001340878.1:p.Arg1234Gln
NP_001340879.1:p.Arg1234Gln
NP_001340880.1:p.Arg1234Gln
NP_001340881.1:p.Arg1234Gln
NP_001340883.1:p.Arg1233Gln
NP_001340884.1:p.Arg1233Gln
NP_001340886.1:p.Arg1217Gln
NP_001340887.1:p.Arg1217Gln
NP_001340889.1:p.Arg1216Gln
NP_001340890.1:p.Arg431Gln
NP_008851.3:p.Arg1234Gln
LRG_8t1:c.3701G>A
LRG_8:g.66386G>A
NC_000002.11:g.166868764C>T
NM_001165963.1:c.3734G>A
NM_006920.4:c.3701G>A
NR_148667.2:n.4087G>A

Protein change:

R1216Q

Links:

UniProtKB/Swiss-Prot: VAR_064311; dbSNP: rs121917912

NCBI 1000 Genomes Browser:

rs121917912

Molecular consequence:

NM_001165963.4:c.3734G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.3650G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.3734G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.3734G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.3701G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.3701G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.3701G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.3701G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.3698G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.3698G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.3650G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.3650G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.3647G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.1292G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.3701G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.4087G>A - 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

CNE_RS39850 [Cupriavidus necator N-1]
CNE_RS39850 [Cupriavidus necator N-1]
Gene ID:34312633

Gene
ccmH [Shigella boydii]
ccmH [Shigella boydii]
Gene ID:58388765

Gene
Compound Links for PMC (Select 2683872) (3)
PubChem Compound
ts96a09.x1 NCI_CGAP_GC6 Homo sapiens cDNA clone IMAGE:2239096 3', mRNA sequence
ts96a09.x1 NCI_CGAP_GC6 Homo sapiens cDNA clone IMAGE:2239096 3', mRNA sequence
gi|4684672|gnl|dbEST|2452146|gb|AI6 .1|

Nucleotide
Hydrogenoanaerobacterium saccharovorans strain:DSM 24774
Hydrogenoanaerobacterium saccharovorans strain:DSM 24774
Hydrogenoanaerobacterium saccharovorans DSM 24774 genome sequencing

BioProject

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
SCV000757826	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 16, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17054684, 21906962, 28202706, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000757826

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 16, 2023)

germline

clinical testing

PubMed (4)
[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

Familial occurrence of febrile seizures and epilepsy in severe myoclonic epilepsy of infancy (SMEI) patients with SCN1A mutations.

Mancardi MM, Striano P, Gennaro E, Madia F, Paravidino R, Scapolan S, Dalla Bernardina B, Bertini E, Bianchi A, Capovilla G, Darra F, Elia M, Freri E, Gobbi G, Granata T, Guerrini R, Pantaleoni C, Parmeggiani A, Romeo A, Santucci M, Vecchi M, Veggiotti P, et al.

Epilepsia. 2006 Oct;47(10):1629-35. Erratum in: Epilepsia. 2007 Feb;48(2):409.

PubMed [citation]

PMID:: 17054684

Dravet syndrome: patients with co-morbid SCN1A gene mutations and mitochondrial electron transport chain defects.

Craig AK, de Menezes MS, Saneto RP.

Seizure. 2012 Jan;21(1):17-20. doi: 10.1016/j.seizure.2011.08.010. Epub 2011 Sep 8.

PubMed [citation]

PMID:: 21906962

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000757826.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1245 of the SCN1A protein (p.Arg1245Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with severe myoclonic epilepsy of infancy (PMID: 17054684, 21906962, 28202706). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68533). 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. For these reasons, this variant has been classified as Pathogenic.

#	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 16, 2024

ClinVar

Relating variation to medicine