NM_001165963.4(SCN1A):c.3667T>G (p.Phe1223Val) AND Early infantile epileptic encephalopathy with suppression bursts

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 19, 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:: RCV002300330.3

Allele description

NM_001165963.4(SCN1A):c.3667T>G (p.Phe1223Val)

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.3667T>G (p.Phe1223Val)

HGVS:

NC_000002.12:g.166013782A>C
NG_011906.1:g.64858T>G
NM_001165963.4:c.3667T>GMANE SELECT
NM_001165964.3:c.3583T>G
NM_001202435.3:c.3667T>G
NM_001353948.2:c.3667T>G
NM_001353949.2:c.3634T>G
NM_001353950.2:c.3634T>G
NM_001353951.2:c.3634T>G
NM_001353952.2:c.3634T>G
NM_001353954.2:c.3631T>G
NM_001353955.2:c.3631T>G
NM_001353957.2:c.3583T>G
NM_001353958.2:c.3583T>G
NM_001353960.2:c.3580T>G
NM_001353961.2:c.1225T>G
NM_006920.6:c.3634T>G
NP_001159435.1:p.Phe1223Val
NP_001159436.1:p.Phe1195Val
NP_001189364.1:p.Phe1223Val
NP_001340877.1:p.Phe1223Val
NP_001340878.1:p.Phe1212Val
NP_001340879.1:p.Phe1212Val
NP_001340880.1:p.Phe1212Val
NP_001340881.1:p.Phe1212Val
NP_001340883.1:p.Phe1211Val
NP_001340884.1:p.Phe1211Val
NP_001340886.1:p.Phe1195Val
NP_001340887.1:p.Phe1195Val
NP_001340889.1:p.Phe1194Val
NP_001340890.1:p.Phe409Val
NP_008851.3:p.Phe1212Val
NP_008851.3:p.Phe1212Val
LRG_8t1:c.3634T>G
LRG_8:g.64858T>G
LRG_8p1:p.Phe1212Val
NC_000002.11:g.166870292A>C
NM_006920.4:c.3634T>G
NR_148667.2:n.4020T>G

Protein change:

F1194V

Molecular consequence:

NM_001165963.4:c.3667T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.3583T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.3667T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.3667T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.3634T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.3634T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.3634T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.3634T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.3631T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.3631T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.3583T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.3583T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.3580T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.1225T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.3634T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.4020T>G - 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
SCV002598428	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 19, 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

SCV002598428

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 19, 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002598428.3

#	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. 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 SCN1A protein function. 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 phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1223 of the SCN1A protein (p.Phe1223Val).

#	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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