NM_001165963.4(SCN1A):c.1186G>A (p.Gly396Arg) AND Severe myoclonic epilepsy in infancy

Germline classification:: Pathogenic (1 submission)
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:: RCV003314358.1

Allele description [Variation Report for NM_001165963.4(SCN1A):c.1186G>A (p.Gly396Arg)]

NM_001165963.4(SCN1A):c.1186G>A (p.Gly396Arg)

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.1186G>A (p.Gly396Arg)

HGVS:

NC_000002.12:g.166046961C>T
NG_011906.1:g.31679G>A
NM_001165963.4:c.1186G>AMANE SELECT
NM_001165964.3:c.1186G>A
NM_001202435.3:c.1186G>A
NM_001353948.2:c.1186G>A
NM_001353949.2:c.1186G>A
NM_001353950.2:c.1186G>A
NM_001353951.2:c.1186G>A
NM_001353952.2:c.1186G>A
NM_001353954.2:c.1186G>A
NM_001353955.2:c.1186G>A
NM_001353957.2:c.1186G>A
NM_001353958.2:c.1186G>A
NM_001353960.2:c.1186G>A
NM_001353961.2:c.-1240G>A
NM_006920.6:c.1186G>A
NP_001159435.1:p.Gly396Arg
NP_001159436.1:p.Gly396Arg
NP_001189364.1:p.Gly396Arg
NP_001340877.1:p.Gly396Arg
NP_001340878.1:p.Gly396Arg
NP_001340879.1:p.Gly396Arg
NP_001340880.1:p.Gly396Arg
NP_001340881.1:p.Gly396Arg
NP_001340883.1:p.Gly396Arg
NP_001340884.1:p.Gly396Arg
NP_001340886.1:p.Gly396Arg
NP_001340887.1:p.Gly396Arg
NP_001340889.1:p.Gly396Arg
NP_008851.3:p.Gly396Arg
NP_008851.3:p.Gly396Arg
LRG_8t1:c.1186G>A
LRG_8:g.31679G>A
LRG_8p1:p.Gly396Arg
NC_000002.11:g.166903471C>T
NM_006920.4:c.1186G>A
NR_148667.2:n.1572G>A

Protein change:

G396R

Molecular consequence:

NM_001353961.2:c.-1240G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.1572G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Severe myoclonic epilepsy in infancy (DRVT)
Synonyms:: Epilepsy, Myoclonic, Infantile, Severe; Dravet syndrome; Epileptic encephalopathy, early infantile, 6 (Dravet syndrome); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100135; MedGen: C0751122; Orphanet: 33069; OMIM: 607208

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004013637	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 35074891, 21868258, 35087721, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004013637

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

unknown

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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Development and Validation of a Prediction Model for Early Diagnosis of SCN1A-Related Epilepsies.

Brunklaus A, Pérez-Palma E, Ghanty I, Xinge J, Brilstra E, Ceulemans B, Chemaly N, de Lange I, Depienne C, Guerrini R, Mei D, Møller RS, Nabbout R, Regan BM, Schneider AL, Scheffer IE, Schoonjans AS, Symonds JD, Weckhuysen S, Kattan MW, Zuberi SM, Lal D.

Neurology. 2022 Mar 15;98(11):e1163-e1174. doi: 10.1212/WNL.0000000000200028. Epub 2022 Jan 24.

PubMed [citation]

PMID:: 35074891
PMCID:: PMC8935441

SCN1A mutational analysis in Korean patients with Dravet syndrome.

Lim BC, Hwang H, Chae JH, Choi JE, Hwang YS, Kang SH, Ki CS, Kim KJ.

Seizure. 2011 Dec;20(10):789-94. doi: 10.1016/j.seizure.2011.08.002. Epub 2011 Aug 24.

PubMed [citation]

PMID:: 21868258

See all PubMed Citations (4)

Details of each submission

From 3billion, SCV004013637.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.96; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SCN1A related disorder (PMID: 35087721). The variant has been previously reported as de novo in a similarly affected individual (PMID: 35087721). Different missense changes at the same codon (p.Gly396Glu, p.Gly396Trp) have been reported to be associated with SCN1A related disorder (PMID: 21868258, 35074891). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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