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NM_001165963.4(SCN1A):c.777C>A (p.Ser259Arg) AND Severe myoclonic epilepsy in infancy

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Jun 10, 2022
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:
RCV000059553.7

Allele description [Variation Report for NM_001165963.4(SCN1A):c.777C>A (p.Ser259Arg)]

NM_001165963.4(SCN1A):c.777C>A (p.Ser259Arg)

Gene:
SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001165963.4(SCN1A):c.777C>A (p.Ser259Arg)
HGVS:
  • NC_000002.12:g.166051906G>T
  • NG_011906.1:g.26734C>A
  • NM_001165963.4:c.777C>AMANE SELECT
  • NM_001165964.3:c.777C>A
  • NM_001202435.3:c.777C>A
  • NM_001353948.2:c.777C>A
  • NM_001353949.2:c.777C>A
  • NM_001353950.2:c.777C>A
  • NM_001353951.2:c.777C>A
  • NM_001353952.2:c.777C>A
  • NM_001353954.2:c.777C>A
  • NM_001353955.2:c.777C>A
  • NM_001353957.2:c.777C>A
  • NM_001353958.2:c.777C>A
  • NM_001353960.2:c.777C>A
  • NM_001353961.2:c.-1649C>A
  • NM_006920.6:c.777C>A
  • NP_001159435.1:p.Ser259Arg
  • NP_001159436.1:p.Ser259Arg
  • NP_001189364.1:p.Ser259Arg
  • NP_001340877.1:p.Ser259Arg
  • NP_001340878.1:p.Ser259Arg
  • NP_001340879.1:p.Ser259Arg
  • NP_001340880.1:p.Ser259Arg
  • NP_001340881.1:p.Ser259Arg
  • NP_001340883.1:p.Ser259Arg
  • NP_001340884.1:p.Ser259Arg
  • NP_001340886.1:p.Ser259Arg
  • NP_001340887.1:p.Ser259Arg
  • NP_001340889.1:p.Ser259Arg
  • NP_008851.3:p.Ser259Arg
  • LRG_8t1:c.777C>A
  • LRG_8:g.26734C>A
  • NC_000002.11:g.166908416G>T
  • NM_001165963.1:c.777C>A
  • NM_001165963.3:c.777C>A
  • NM_006920.4:c.777C>A
  • NR_148667.2:n.1163C>A
  • P35498:p.Ser259Arg
Protein change:
S259R
Links:
UniProtKB: P35498#VAR_064240; UniProtKB/Swiss-Prot: VAR_064240; dbSNP: rs121918735
NCBI 1000 Genomes Browser:
rs121918735
Molecular consequence:
  • NM_001353961.2:c.-1649C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001165963.4:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.777C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.1163C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Severe myoclonic epilepsy in infancy (DRVT)
Synonyms:
Epilepsy, Myoclonic, Infantile, Severe; SEVERE MYOCLONIC EPILEPSY OF INFANCY; Dravet syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0100135; MedGen: C0751122; Orphanet: 33069; OMIM: 607208

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000091085UniProtKB/Swiss-Prot
no classification provided
not providedgermlinenot provided

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

SCV000221859Center for Bioinformatics, Peking University - University Clinical Cooperation “985 Project” PKU-2014-1-1

See additional submitters

criteria provided, single submitter

(Xu et al. (Hum Mutat. 2015))		Pathogenic
(Dec 20, 2014) 		de novoresearch

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

Citation Link,

SCV002526397DASA
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jun 10, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot provided1not providedliterature only
Chinesede novoyes1not providednot providednot providednot providedresearch

Citations

PubMed

Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "de novo" SCN1A Mutations in Children with Dravet Syndrome.

Xu X, Yang X, Wu Q, Liu A, Yang X, Ye AY, Huang AY, Li J, Wang M, Yu Z, Wang S, Zhang Z, Wu X, Wei L, Zhang Y.

Hum Mutat. 2015 Sep;36(9):861-72. doi: 10.1002/humu.22819. Epub 2015 Jul 24.

PubMed [citation]
PMID:
26096185
PMCID:
PMC5034833

Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome.

Sun H, Zhang Y, Liu X, Ma X, Yang Z, Qin J, Jiang Y, Qi Y, Wu X.

J Hum Genet. 2010 Jul;55(7):421-7. doi: 10.1038/jhg.2010.39. Epub 2010 Apr 30.

PubMed [citation]
PMID:
20431604
See all PubMed Citations (4)

Details of each submission

From UniProtKB/Swiss-Prot, SCV000091085.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot provided PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot provided1not providednot providednot providednot providednot providednot provided

From Center for Bioinformatics, Peking University - University Clinical Cooperation “985 Project” PKU-2014-1-1, SCV000221859.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Chinese1not providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot provided1not providednot providednot provided

From DASA, SCV002526397.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The c.777C>A;p.(Ser259Arg) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 68673; PMID: 20431604; 30735520) - PS4.Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 30735520) - PS3_supporting. This variant is not present in population databases:rs121918735 , gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID: 20431604; 30735520)PM6. In summary, the currently available evidence indicates that the variant is Likely Pathogenic

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Apr 13, 2025