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NM_001165963.4(SCN1A):c.4453A>G (p.Asn1485Asp) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 2, 2022
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:
RCV000636398.7

Allele description [Variation Report for NM_001165963.4(SCN1A):c.4453A>G (p.Asn1485Asp)]

NM_001165963.4(SCN1A):c.4453A>G (p.Asn1485Asp)

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.4453A>G (p.Asn1485Asp)
HGVS:
  • NC_000002.12:g.165998061T>C
  • NG_011906.1:g.80579A>G
  • NM_001165963.4:c.4453A>GMANE SELECT
  • NM_001165964.3:c.4369A>G
  • NM_001202435.3:c.4453A>G
  • NM_001353948.2:c.4453A>G
  • NM_001353949.2:c.4420A>G
  • NM_001353950.2:c.4420A>G
  • NM_001353951.2:c.4420A>G
  • NM_001353952.2:c.4420A>G
  • NM_001353954.2:c.4417A>G
  • NM_001353955.2:c.4417A>G
  • NM_001353957.2:c.4369A>G
  • NM_001353958.2:c.4369A>G
  • NM_001353960.2:c.4366A>G
  • NM_001353961.2:c.2011A>G
  • NM_006920.6:c.4420A>G
  • NP_001159435.1:p.Asn1485Asp
  • NP_001159436.1:p.Asn1457Asp
  • NP_001189364.1:p.Asn1485Asp
  • NP_001340877.1:p.Asn1485Asp
  • NP_001340878.1:p.Asn1474Asp
  • NP_001340879.1:p.Asn1474Asp
  • NP_001340880.1:p.Asn1474Asp
  • NP_001340881.1:p.Asn1474Asp
  • NP_001340883.1:p.Asn1473Asp
  • NP_001340884.1:p.Asn1473Asp
  • NP_001340886.1:p.Asn1457Asp
  • NP_001340887.1:p.Asn1457Asp
  • NP_001340889.1:p.Asn1456Asp
  • NP_001340890.1:p.Asn671Asp
  • NP_008851.3:p.Asn1474Asp
  • LRG_8:g.80579A>G
  • NC_000002.11:g.166854571T>C
  • NM_001165963.1:c.4453A>G
  • NR_148667.2:n.4870A>G
Protein change:
N1456D
Links:
dbSNP: rs1553522331
NCBI 1000 Genomes Browser:
rs1553522331
Molecular consequence:
  • NM_001165963.4:c.4453A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.4369A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.4453A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.4453A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.4420A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.4420A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.4420A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.4420A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.4417A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.4417A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.4369A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.4369A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.4366A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.2011A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.4420A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.4870A>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000757837Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 2, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, et al.

Nat Genet. 2013 Jul;45(7):825-30. doi: 10.1038/ng.2646. Epub 2013 May 26.

PubMed [citation]
PMID:
23708187
PMCID:
PMC3704157

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000757837.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 530510). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 23708187). 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 aspartic acid, which is acidic and polar, at codon 1485 of the SCN1A protein (p.Asn1485Asp).

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

Last Updated: Feb 20, 2024