NM_001165963.4(SCN1A):c.5347G>A (p.Ala1783Thr) AND Generalized epilepsy with febrile seizures plus, type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 5, 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:: RCV001849308.11

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5347G>A (p.Ala1783Thr)]

NM_001165963.4(SCN1A):c.5347G>A (p.Ala1783Thr)

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.5347G>A (p.Ala1783Thr)

Other names:

p.A1783T:GCG>ACG

HGVS:

NC_000002.12:g.165991928C>T
NG_011906.1:g.86712G>A
NM_001165963.4:c.5347G>AMANE SELECT
NM_001165964.3:c.5263G>A
NM_001202435.3:c.5347G>A
NM_001353948.2:c.5347G>A
NM_001353949.2:c.5314G>A
NM_001353950.2:c.5314G>A
NM_001353951.2:c.5314G>A
NM_001353952.2:c.5314G>A
NM_001353954.2:c.5311G>A
NM_001353955.2:c.5311G>A
NM_001353957.2:c.5263G>A
NM_001353958.2:c.5263G>A
NM_001353960.2:c.5260G>A
NM_001353961.2:c.2905G>A
NM_006920.6:c.5314G>A
NP_001159435.1:p.Ala1783Thr
NP_001159435.1:p.Ala1783Thr
NP_001159436.1:p.Ala1755Thr
NP_001189364.1:p.Ala1783Thr
NP_001340877.1:p.Ala1783Thr
NP_001340878.1:p.Ala1772Thr
NP_001340879.1:p.Ala1772Thr
NP_001340880.1:p.Ala1772Thr
NP_001340881.1:p.Ala1772Thr
NP_001340883.1:p.Ala1771Thr
NP_001340884.1:p.Ala1771Thr
NP_001340886.1:p.Ala1755Thr
NP_001340887.1:p.Ala1755Thr
NP_001340889.1:p.Ala1754Thr
NP_001340890.1:p.Ala969Thr
NP_008851.3:p.Ala1772Thr
LRG_8t1:c.5314G>A
LRG_8:g.86712G>A
NC_000002.11:g.166848438C>T
NM_001165963.1:c.5347G>A
NM_001165963.2:c.5347G>A
NM_006920.4:c.5314G>A
NR_148667.2:n.5764G>A

Protein change:

A1754T

Links:

UniProtKB/Swiss-Prot: VAR_064275; dbSNP: rs121917980

NCBI 1000 Genomes Browser:

rs121917980

Molecular consequence:

NM_001165963.4:c.5347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001165964.3:c.5263G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001202435.3:c.5347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353948.2:c.5347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353949.2:c.5314G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353950.2:c.5314G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353951.2:c.5314G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353952.2:c.5314G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353954.2:c.5311G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353955.2:c.5311G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353957.2:c.5263G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353958.2:c.5263G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353960.2:c.5260G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001353961.2:c.2905G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006920.6:c.5314G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148667.2:n.5764G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Generalized epilepsy with febrile seizures plus, type 2 (GEFSP2)
Synonyms:: GEFS+, TYPE 2
Identifiers:: MONDO: MONDO:0011461; MedGen: C1858673; Orphanet: 36387; OMIM: 604403

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002107108	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 5, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 30321769, 22071555, 19589774, 17347258, 26096185, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002107108

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 5, 2022)

germline

clinical testing

PubMed (6)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Dravet syndrome in South African infants: Tools for an early diagnosis.

Esterhuizen AI, Mefford HC, Ramesar RS, Wang S, Carvill GL, Wilmshurst JM.

Seizure. 2018 Nov;62:99-105. doi: 10.1016/j.seizure.2018.09.010. Epub 2018 Sep 14.

PubMed [citation]

PMID:: 30321769
PMCID:: PMC6261486

Early clinical features in Dravet syndrome patients with and without SCN1A mutations.

Petrelli C, Passamonti C, Cesaroni E, Mei D, Guerrini R, Zamponi N, Provinciali L.

Epilepsy Res. 2012 Mar;99(1-2):21-7. doi: 10.1016/j.eplepsyres.2011.10.010. Epub 2011 Nov 8.

PubMed [citation]

PMID:: 22071555

See all PubMed Citations (6)

Details of each submission

From DASA, SCV002107108.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (6)

Description

The c.5347G>A;p.(Ala1783Thr) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 68570; PMID: 30321769; PMID: 26096185; PMID: 17347258; PMID: 22071555; PMID: 19589774) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Ion_trans;PKD_channel) - PM1. This variant is not present in population databases (rs121917980- gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. Pathogenic missense variant in this residue have been reported (ClinVar ID: 68571) - PM5. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID: 17347258) - PM6. The variant co-segregated with disease in multiple affected family members (PMID: 26096185) - PP1. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic.

#	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		1	not provided	not provided	not provided

Last Updated: Apr 20, 2024

ClinVar

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