NM_001165963.4(SCN1A):c.5348C>T (p.Ala1783Val) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Feb 20, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000189000.10

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]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000242631	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 20, 2024)	germline	clinical testing	Citation Link,
SCV000341355	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Jun 2, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV004026438	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 26, 2023)	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

SCV000242631

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 20, 2024)

germline

clinical testing

Citation Link,

SCV000341355

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Jun 2, 2016)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV004026438

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 26, 2023)

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	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000242631.12

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

Description

A different missense change at this residue (p.A1755T) has been reported in the published literature and at GeneDx in association with SCN1A-related epilepsy (PMID: 20431604, 17347258); Published functional studies demonstrate that this variant significantly affects activation and slow inactivation properties of SCN1A NaV1.1 channels (PMID: 34776868); This substitution is predicted to be within the transmembrane segment S6 of the fourth homologous domain; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21703448, 29056246, 30368457, 32090326, 29573403, 33902251, 35074891, 30552426, 17561957, 34776868, 29460957, 20431604, 17347258)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000341355.5

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

#	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		1	not provided	not provided	not provided

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV004026438.1

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

Description

PM1, PP3, PM5, PP2, PS4, PM2_SUP

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 14, 2025

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