NM_001165963.4(SCN1A):c.5309T>A (p.Ile1770Asn) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 19, 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:: RCV003588453.2

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5309T>A (p.Ile1770Asn)]

NM_001165963.4(SCN1A):c.5309T>A (p.Ile1770Asn)

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.5309T>A (p.Ile1770Asn)

HGVS:

NC_000002.12:g.165991966A>T
NG_011906.1:g.86674T>A
NM_001165963.4:c.5309T>AMANE SELECT
NM_001165964.3:c.5225T>A
NM_001202435.3:c.5309T>A
NM_001353948.2:c.5309T>A
NM_001353949.2:c.5276T>A
NM_001353950.2:c.5276T>A
NM_001353951.2:c.5276T>A
NM_001353952.2:c.5276T>A
NM_001353954.2:c.5273T>A
NM_001353955.2:c.5273T>A
NM_001353957.2:c.5225T>A
NM_001353958.2:c.5225T>A
NM_001353960.2:c.5222T>A
NM_001353961.2:c.2867T>A
NM_006920.6:c.5276T>A
NP_001159435.1:p.Ile1770Asn
NP_001159436.1:p.Ile1742Asn
NP_001189364.1:p.Ile1770Asn
NP_001340877.1:p.Ile1770Asn
NP_001340878.1:p.Ile1759Asn
NP_001340879.1:p.Ile1759Asn
NP_001340880.1:p.Ile1759Asn
NP_001340881.1:p.Ile1759Asn
NP_001340883.1:p.Ile1758Asn
NP_001340884.1:p.Ile1758Asn
NP_001340886.1:p.Ile1742Asn
NP_001340887.1:p.Ile1742Asn
NP_001340889.1:p.Ile1741Asn
NP_001340890.1:p.Ile956Asn
NP_008851.3:p.Ile1759Asn
NP_008851.3:p.Ile1759Asn
LRG_8t1:c.5276T>A
LRG_8:g.86674T>A
LRG_8p1:p.Ile1759Asn
NC_000002.11:g.166848476A>T
NM_006920.4:c.5276T>A
NR_148667.2:n.5726T>A

Protein change:

I1741N

Molecular consequence:

NM_001165963.4:c.5309T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.5225T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.5309T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.5309T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.5276T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.5276T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.5276T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.5276T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.5273T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.5273T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.5225T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.5225T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.5222T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.2867T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.5276T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.5726T>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293420	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 19, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32090326, 34106054, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293420

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 19, 2023)

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

Biological concepts in human sodium channel epilepsies and their relevance in clinical practice.

Brunklaus A, Du J, Steckler F, Ghanty II, Johannesen KM, Fenger CD, Schorge S, Baez-Nieto D, Wang HR, Allen A, Pan JQ, Lerche H, Heyne H, Symonds JD, Zuberi SM, Sanders S, Sheidley BR, Craiu D, Olson HE, Weckhuysen S, DeJonge P, Helbig I, et al.

Epilepsia. 2020 Mar;61(3):387-399. doi: 10.1111/epi.16438. Epub 2020 Feb 23.

PubMed [citation]

PMID:: 32090326

Focal epilepsy due to de novo SCN1A mutation.

Laur D, Dozières-Puyravel B, Iléa A, Nava C, Delanoë C, Nasser H, Le Guern E, Auvin S.

Epileptic Disord. 2021 Jun 1;23(3):459-465. doi: 10.1684/epd.2021.1285.

PubMed [citation]

PMID:: 34106054

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004293420.1

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

Description

For these reasons, this variant has been classified as Pathogenic. 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 missense change has been observed in individual(s) with SCN1A-related epilepsy (PMID: 32090326, 34106054). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 1770 of the SCN1A protein (p.Ile1770Asn).

#	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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