NM_001165963.4(SCN1A):c.640G>A (p.Ala214Thr) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 2018
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:: RCV000819574.8

Allele description [Variation Report for NM_001165963.4(SCN1A):c.640G>A (p.Ala214Thr)]

NM_001165963.4(SCN1A):c.640G>A (p.Ala214Thr)

Gene:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.640G>A (p.Ala214Thr)

HGVS:

NC_000002.12:g.166052906C>T
NG_011906.1:g.25734G>A
NM_001165963.4:c.640G>AMANE SELECT
NM_001165964.3:c.640G>A
NM_001202435.3:c.640G>A
NM_001353948.2:c.640G>A
NM_001353949.2:c.640G>A
NM_001353950.2:c.640G>A
NM_001353951.2:c.640G>A
NM_001353952.2:c.640G>A
NM_001353954.2:c.640G>A
NM_001353955.2:c.640G>A
NM_001353957.2:c.640G>A
NM_001353958.2:c.640G>A
NM_001353960.2:c.640G>A
NM_001353961.2:c.-1786G>A
NM_006920.6:c.640G>A
NP_001159435.1:p.Ala214Thr
NP_001159436.1:p.Ala214Thr
NP_001189364.1:p.Ala214Thr
NP_001340877.1:p.Ala214Thr
NP_001340878.1:p.Ala214Thr
NP_001340879.1:p.Ala214Thr
NP_001340880.1:p.Ala214Thr
NP_001340881.1:p.Ala214Thr
NP_001340883.1:p.Ala214Thr
NP_001340884.1:p.Ala214Thr
NP_001340886.1:p.Ala214Thr
NP_001340887.1:p.Ala214Thr
NP_001340889.1:p.Ala214Thr
NP_008851.3:p.Ala214Thr
LRG_8:g.25734G>A
NC_000002.11:g.166909416C>T
NM_001165963.1:c.640G>A
NR_148667.2:n.1026G>A

Protein change:

A214T

Links:

dbSNP: rs1574272597

NCBI 1000 Genomes Browser:

rs1574272597

Molecular consequence:

NM_001353961.2:c.-1786G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001165963.4:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.1026G>A - 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

Recent activity

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polypeptide N-acetylgalactosaminyltransferase 16 isoform X1 [Homo sapiens]
polypeptide N-acetylgalactosaminyltransferase 16 isoform X1 [Homo sapiens]
gi|2462541042|ref|XP_054232424.1|

Protein
polypeptide N-acetylgalactosaminyltransferase 16 isoform X2 [Homo sapiens]
polypeptide N-acetylgalactosaminyltransferase 16 isoform X2 [Homo sapiens]
gi|2462541044|ref|XP_054232425.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000960242	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 25, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25348405, 18804930, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000960242

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 25, 2018)

germline

clinical testing

PubMed (3)
[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

UniProt: a hub for protein information.

UniProt Consortium..

Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12. doi: 10.1093/nar/gku989. Epub 2014 Oct 27.

PubMed [citation]

PMID:: 25348405
PMCID:: PMC4384041

A catalog of SCN1A variants.

Lossin C.

Brain Dev. 2009 Feb;31(2):114-30. doi: 10.1016/j.braindev.2008.07.011. Epub 2008 Sep 19. Review. Erratum in: Brain Dev. 2014 Jan;36(1):90.

PubMed [citation]

PMID:: 18804930

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000960242.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant identified in the SCN1A gene is located in the transmembrane D1-S4 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SCN1A-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 214 of the SCN1A protein (p.Ala214Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.

#	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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