NM_001330260.2(SCN8A):c.632T>G (p.Val211Gly) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 5, 2021
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:: RCV001922799.5

Allele description [Variation Report for NM_001330260.2(SCN8A):c.632T>G (p.Val211Gly)]

NM_001330260.2(SCN8A):c.632T>G (p.Val211Gly)

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.632T>G (p.Val211Gly)

HGVS:

NC_000012.12:g.51689022T>G
NG_021180.3:g.104065T>G
NM_001177984.3:c.706+173T>G
NM_001330260.1:c.632T>G
NM_001330260.2:c.632T>GMANE SELECT
NM_001369788.1:c.632T>G
NM_014191.4:c.706+173T>G
NP_001317189.1:p.Val211Gly
NP_001356717.1:p.Val211Gly
LRG_1389t1:c.632T>G
LRG_1389t2:c.706+173T>G
LRG_1389:g.104065T>G
LRG_1389p1:p.Val211Gly
NC_000012.11:g.52082806T>G

Protein change:

V211G

Links:

dbSNP: rs1592380834

NCBI 1000 Genomes Browser:

rs1592380834

Molecular consequence:

NM_001177984.3:c.706+173T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_014191.4:c.706+173T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330260.2:c.632T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.632T>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

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MEF2C-AS1 MEF2C antisense RNA 1 [Homo sapiens]
MEF2C-AS1 MEF2C antisense RNA 1 [Homo sapiens]
Gene ID:101929423

Gene
Gene Links for GEO Profiles (Select 109427174) (1)
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Profile neighbors for GEO Profiles (Select 85938317) (16)
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Chromosome neighbors for GEO Profiles (Select 89647888) (21)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002171802	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 5, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30951195, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002171802

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 5, 2021)

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 Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield.

Epilepsy Genetics Initiative..

Epilepsia. 2019 May;60(5):797-806. doi: 10.1111/epi.14698. Epub 2019 Apr 5.

PubMed [citation]

PMID:: 30951195
PMCID:: PMC6519344

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, SCV002171802.3

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

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val211 (p.Val9 in the literature) amino acid residue in SCN8A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30951195). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This missense change has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. This sequence change replaces valine with glycine at codon 211 of the SCN8A protein (p.Val211Gly). The SCN8A gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001330260.1, and corresponds to NM_014191.3:c.706+173T>G in the primary transcript.

#	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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