NM_001330260.2(SCN8A):c.685A>G (p.Lys229Glu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 23, 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:: RCV001428051.8

Allele description [Variation Report for NM_001330260.2(SCN8A):c.685A>G (p.Lys229Glu)]

NM_001330260.2(SCN8A):c.685A>G (p.Lys229Glu)

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.685A>G (p.Lys229Glu)

HGVS:

NC_000012.12:g.51689075A>G
NG_021180.3:g.104118A>G
NM_001177984.3:c.706+226A>G
NM_001330260.2:c.685A>GMANE SELECT
NM_001369788.1:c.685A>G
NM_014191.4:c.706+226A>G
NP_001317189.1:p.Lys229Glu
NP_001356717.1:p.Lys229Glu
LRG_1389t1:c.685A>G
LRG_1389t2:c.706+226A>G
LRG_1389:g.104118A>G
LRG_1389p1:p.Lys229Glu
NC_000012.11:g.52082859A>G

Protein change:

K229E

Links:

dbSNP: rs2138716740

NCBI 1000 Genomes Browser:

rs2138716740

Molecular consequence:

NM_001177984.3:c.706+226A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_014191.4:c.706+226A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330260.2:c.685A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.685A>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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LOC129997603 [Homo sapiens]
LOC129997603 [Homo sapiens]
Gene ID:129997603

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LOC126859837 [Homo sapiens]
LOC126859837 [Homo sapiens]
Gene ID:126859837

Gene
LOC129997258 [Homo sapiens]
LOC129997258 [Homo sapiens]
Gene ID:129997258

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LOC129997297 [Homo sapiens]
LOC129997297 [Homo sapiens]
Gene ID:129997297

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LOC103352541 [Homo sapiens]
LOC103352541 [Homo sapiens]
Gene ID:103352541

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001630743	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 23, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001630743

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 23, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001630743.4

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1104115). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 229 of the SCN8A protein (p.Lys229Glu). 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+226A>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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