NM_001165963.4(SCN1A):c.5348C>T (p.Ala1783Val) AND Developmental and epileptic encephalopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 12, 2024
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:: RCV001207693.10

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5348C>T (p.Ala1783Val)]

NM_001165963.4(SCN1A):c.5348C>T (p.Ala1783Val)

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.5348C>T (p.Ala1783Val)

Other names:

p.A1783V:GCG>GTG

HGVS:

NC_000002.12:g.165991927G>A
NG_011906.1:g.86713C>T
NM_001165963.4:c.5348C>TMANE SELECT
NM_001165964.3:c.5264C>T
NM_001202435.3:c.5348C>T
NM_001353948.2:c.5348C>T
NM_001353949.2:c.5315C>T
NM_001353950.2:c.5315C>T
NM_001353951.2:c.5315C>T
NM_001353952.2:c.5315C>T
NM_001353954.2:c.5312C>T
NM_001353955.2:c.5312C>T
NM_001353957.2:c.5264C>T
NM_001353958.2:c.5264C>T
NM_001353960.2:c.5261C>T
NM_001353961.2:c.2906C>T
NM_006920.6:c.5315C>T
NP_001159435.1:p.Ala1783Val
NP_001159436.1:p.Ala1755Val
NP_001189364.1:p.Ala1783Val
NP_001340877.1:p.Ala1783Val
NP_001340878.1:p.Ala1772Val
NP_001340879.1:p.Ala1772Val
NP_001340880.1:p.Ala1772Val
NP_001340881.1:p.Ala1772Val
NP_001340883.1:p.Ala1771Val
NP_001340884.1:p.Ala1771Val
NP_001340886.1:p.Ala1755Val
NP_001340887.1:p.Ala1755Val
NP_001340889.1:p.Ala1754Val
NP_001340890.1:p.Ala969Val
NP_008851.3:p.Ala1772Val
LRG_8t1:c.5315C>T
LRG_8:g.86713C>T
NC_000002.11:g.166848437G>A
NM_001165963.1:c.5348C>T
NM_006920.4:c.5315C>T
NR_148667.2:n.5765C>T

Protein change:

A1754V

Links:

UniProtKB/Swiss-Prot: VAR_064345; dbSNP: rs121917921

NCBI 1000 Genomes Browser:

rs121917921

Molecular consequence:

NM_001165963.4:c.5348C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.5264C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.5348C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.5348C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.5315C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.5315C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.5315C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.5315C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.5312C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.5312C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.5264C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.5264C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.5261C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.2906C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.5315C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.5765C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C5779964; OMIM: PS308350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001379057	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 12, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17561957, 18930999, 29460957, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001379057

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 12, 2024)

germline

clinical testing

PubMed (4)
[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

Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities.

Marini C, Mei D, Temudo T, Ferrari AR, Buti D, Dravet C, Dias AI, Moreira A, Calado E, Seri S, Neville B, Narbona J, Reid E, Michelucci R, Sicca F, Cross HJ, Guerrini R.

Epilepsia. 2007 Sep;48(9):1678-1685. doi: 10.1111/j.1528-1167.2007.01122.x. Epub 2007 Jun 11.

PubMed [citation]

PMID:: 17561957

Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients.

Depienne C, Trouillard O, Saint-Martin C, Gourfinkel-An I, Bouteiller D, Carpentier W, Keren B, Abert B, Gautier A, Baulac S, Arzimanoglou A, Cazeneuve C, Nabbout R, LeGuern E.

J Med Genet. 2009 Mar;46(3):183-91. doi: 10.1136/jmg.2008.062323. Epub 2008 Oct 17.

PubMed [citation]

PMID:: 18930999

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001379057.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1783 of the SCN1A protein (p.Ala1783Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 17561957, 18930999, 29460957). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68571). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#	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: Jun 14, 2025

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