NM_001165963.4(SCN1A):c.3880G>T (p.Val1294Phe) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 3, 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:: RCV001037109.8

Allele description [Variation Report for NM_001165963.4(SCN1A):c.3880G>T (p.Val1294Phe)]

NM_001165963.4(SCN1A):c.3880G>T (p.Val1294Phe)

Genes:

SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001165963.4(SCN1A):c.3880G>T (p.Val1294Phe)

HGVS:

NC_000002.12:g.166009841C>A
NG_011906.1:g.68799G>T
NM_001165963.4:c.3880G>TMANE SELECT
NM_001165963.4:c.3880G>T
NM_001165964.3:c.3796G>T
NM_001202435.3:c.3880G>T
NM_001353948.2:c.3880G>T
NM_001353949.2:c.3847G>T
NM_001353950.2:c.3847G>T
NM_001353951.2:c.3847G>T
NM_001353952.2:c.3847G>T
NM_001353954.2:c.3844G>T
NM_001353955.2:c.3844G>T
NM_001353957.2:c.3796G>T
NM_001353958.2:c.3796G>T
NM_001353960.2:c.3793G>T
NM_001353961.2:c.1438G>T
NM_006920.6:c.3847G>T
NP_001159435.1:p.Val1294Phe
NP_001159436.1:p.Val1266Phe
NP_001189364.1:p.Val1294Phe
NP_001340877.1:p.Val1294Phe
NP_001340878.1:p.Val1283Phe
NP_001340879.1:p.Val1283Phe
NP_001340880.1:p.Val1283Phe
NP_001340881.1:p.Val1283Phe
NP_001340883.1:p.Val1282Phe
NP_001340884.1:p.Val1282Phe
NP_001340886.1:p.Val1266Phe
NP_001340887.1:p.Val1266Phe
NP_001340889.1:p.Val1265Phe
NP_001340890.1:p.Val480Phe
NP_008851.3:p.Val1283Phe
LRG_8:g.68799G>T
NC_000002.11:g.166866351C>A
NM_001165963.1:c.3880G>T
NR_148667.2:n.4233G>T

Protein change:

V1265F

Links:

dbSNP: rs1692186944

NCBI 1000 Genomes Browser:

rs1692186944

Molecular consequence:

NM_001165963.4:c.3880G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.3796G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.3880G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.3880G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.3847G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.3847G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.3847G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.3847G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.3844G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.3844G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.3796G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.3796G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.3793G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.1438G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.3847G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.4233G>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001200507	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 3, 2022)	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

SCV001200507

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 3, 2022)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001200507.5

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

Description

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. 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 may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 836073). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1294 of the SCN1A protein (p.Val1294Phe).

#	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: Feb 20, 2024

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