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NM_001330260.2(SCN8A):c.5302A>G (p.Asn1768Asp) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 23, 2019
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:
RCV001230237.15

Allele description

NM_001330260.2(SCN8A):c.5302A>G (p.Asn1768Asp)

Gene:
SCN8A:sodium voltage-gated channel alpha subunit 8 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_001330260.2(SCN8A):c.5302A>G (p.Asn1768Asp)
HGVS:
  • NC_000012.12:g.51806788A>G
  • NG_021180.3:g.221831A>G
  • NM_001177984.3:c.5179A>G
  • NM_001330260.2:c.5302A>GMANE SELECT
  • NM_001369788.1:c.5179A>G
  • NM_014191.4:c.5302A>G
  • NP_001171455.1:p.Asn1727Asp
  • NP_001317189.1:p.Asn1768Asp
  • NP_001356717.1:p.Asn1727Asp
  • NP_055006.1:p.Asn1768Asp
  • LRG_1389t1:c.5302A>G
  • LRG_1389t2:c.5302A>G
  • LRG_1389:g.221831A>G
  • LRG_1389p1:p.Asn1768Asp
  • LRG_1389p2:p.Asn1768Asp
  • NC_000012.11:g.52200572A>G
  • NM_014191.3:c.5302A>G
  • Q9UQD0:p.Asn1768Asp
Protein change:
N1727D; ASN1768ASP
Links:
UniProtKB: Q9UQD0#VAR_067539; OMIM: 600702.0002; dbSNP: rs202151337
NCBI 1000 Genomes Browser:
rs202151337
Molecular consequence:
  • NM_001177984.3:c.5179A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330260.2:c.5302A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369788.1:c.5179A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014191.4:c.5302A>G - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
  • Increase in persistent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0040]
  • Increase in resurgent current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0099]
  • Overall gain-of-function effect with respect to biophysical channel activity [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0140]
  • Severe depolarizing shift of voltage dependence of fast inactivation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0064]

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
SCV001402711Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 23, 2019) 		germlineclinical testing

PubMed (5)
[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

Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy.

Wagnon JL, Korn MJ, Parent R, Tarpey TA, Jones JM, Hammer MF, Murphy GG, Parent JM, Meisler MH.

Hum Mol Genet. 2015 Jan 15;24(2):506-15. doi: 10.1093/hmg/ddu470. Epub 2014 Sep 16.

PubMed [citation]
PMID:
25227913
PMCID:
PMC4275076

Aberrant Sodium Channel Currents and Hyperexcitability of Medial Entorhinal Cortex Neurons in a Mouse Model of SCN8A Encephalopathy.

Ottolini M, Barker BS, Gaykema RP, Meisler MH, Patel MK.

J Neurosci. 2017 Aug 9;37(32):7643-7655. doi: 10.1523/JNEUROSCI.2709-16.2017. Epub 2017 Jul 4.

PubMed [citation]
PMID:
28676574
PMCID:
PMC5551062
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001402711.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect SCN8A protein function (PMID: 22365152, 25227913, 28676574). This variant has been observed in individual(s) with epileptic encephalopathy (PMID: 22365152, 29186148). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 30123). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with aspartic acid at codon 1768 of the SCN8A protein (p.Asn1768Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid.

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

Last Updated: Sep 16, 2024