NM_001330260.2(SCN8A):c.5401C>G (p.Gln1801Glu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 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:: RCV001059522.15

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5401C>G (p.Gln1801Glu)]

NM_001330260.2(SCN8A):c.5401C>G (p.Gln1801Glu)

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.5401C>G (p.Gln1801Glu)

HGVS:

NC_000012.12:g.51806887C>G
NG_021180.3:g.221930C>G
NM_001177984.3:c.5278C>G
NM_001330260.2:c.5401C>GMANE SELECT
NM_001369788.1:c.5278C>G
NM_014191.4:c.5401C>G
NP_001171455.1:p.Gln1760Glu
NP_001317189.1:p.Gln1801Glu
NP_001356717.1:p.Gln1760Glu
NP_055006.1:p.Gln1801Glu
LRG_1389t1:c.5401C>G
LRG_1389t2:c.5401C>G
LRG_1389:g.221930C>G
LRG_1389p1:p.Gln1801Glu
LRG_1389p2:p.Gln1801Glu
NC_000012.11:g.52200671C>G
NM_014191.3:c.5401C>G
Q9UQD0:p.Gln1801Glu

Protein change:

Q1760E

Links:

UniProtKB: Q9UQD0#VAR_076614; dbSNP: rs879255710

NCBI 1000 Genomes Browser:

rs879255710

Molecular consequence:

NM_001177984.3:c.5278C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.5401C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.5278C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.5401C>G - missense variant - [Sequence Ontology: SO:0001583]

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

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
SCV001224148	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25568300, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001224148

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2022)

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

The phenotypic spectrum of SCN8A encephalopathy.

Larsen J, Carvill GL, Gardella E, Kluger G, Schmiedel G, Barisic N, Depienne C, Brilstra E, Mang Y, Nielsen JE, Kirkpatrick M, Goudie D, Goldman R, Jähn JA, Jepsen B, Gill D, Döcker M, Biskup S, McMahon JM, Koeleman B, Harris M, Braun K, et al.

Neurology. 2015 Feb 3;84(5):480-9. doi: 10.1212/WNL.0000000000001211. Epub 2015 Jan 7.

PubMed [citation]

PMID:: 25568300
PMCID:: PMC4336074

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, SCV001224148.5

#	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) performed at Invitae indicates that this missense variant is expected to disrupt SCN8A protein function. ClinVar contains an entry for this variant (Variation ID: 253295). This missense change has been observed in individual(s) with clinical features of SCN8A-related conditions (PMID: 25568300). 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 glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1801 of the SCN8A protein (p.Gln1801Glu).

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine