NM_001165963.4(SCN1A):c.345T>A (p.Asn115Lys) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 25, 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:: RCV003753168.2

Allele description [Variation Report for NM_001165963.4(SCN1A):c.345T>A (p.Asn115Lys)]

NM_001165963.4(SCN1A):c.345T>A (p.Asn115Lys)

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.345T>A (p.Asn115Lys)

HGVS:

NC_000002.12:g.166058608A>T
NG_011906.1:g.20032T>A
NM_001165963.4:c.345T>AMANE SELECT
NM_001165964.3:c.345T>A
NM_001202435.3:c.345T>A
NM_001353948.2:c.345T>A
NM_001353949.2:c.345T>A
NM_001353950.2:c.345T>A
NM_001353951.2:c.345T>A
NM_001353952.2:c.345T>A
NM_001353954.2:c.345T>A
NM_001353955.2:c.345T>A
NM_001353957.2:c.345T>A
NM_001353958.2:c.345T>A
NM_001353960.2:c.345T>A
NM_001353961.2:c.-2081T>A
NM_006920.6:c.345T>A
NP_001159435.1:p.Asn115Lys
NP_001159436.1:p.Asn115Lys
NP_001189364.1:p.Asn115Lys
NP_001340877.1:p.Asn115Lys
NP_001340878.1:p.Asn115Lys
NP_001340879.1:p.Asn115Lys
NP_001340880.1:p.Asn115Lys
NP_001340881.1:p.Asn115Lys
NP_001340883.1:p.Asn115Lys
NP_001340884.1:p.Asn115Lys
NP_001340886.1:p.Asn115Lys
NP_001340887.1:p.Asn115Lys
NP_001340889.1:p.Asn115Lys
NP_008851.3:p.Asn115Lys
LRG_8:g.20032T>A
NC_000002.11:g.166915118A>T
NC_000002.11:g.166915118A>T
NM_001165963.1:c.345T>A
NR_148667.2:n.731T>A

Protein change:

N115K

Links:

dbSNP: rs61741123

NCBI 1000 Genomes Browser:

rs61741123

Molecular consequence:

NM_001353961.2:c.-2081T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.345T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.731T>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004509247	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 25, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29933521, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004509247

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 25, 2023)

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

Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy.

Peng J, Pang N, Wang Y, Wang XL, Chen J, Xiong J, Peng P, Zhu CH, Kessi MB, He F, Yin F.

CNS Neurosci Ther. 2019 Jan;25(1):14-20. doi: 10.1111/cns.12869. Epub 2018 Jun 22.

PubMed [citation]

PMID:: 29933521
PMCID:: PMC6436594

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, SCV004509247.1

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

Description

For these reasons, this variant has been classified as 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 972887). This missense change has been observed in individual(s) with Dravet syndrome and/or generalized seizures (PMID: 29933521; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 115 of the SCN1A protein (p.Asn115Lys).

#	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

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