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NM_001165963.4(SCN1A):c.4547C>A (p.Ser1516Ter)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Sep 30, 2021)
Last evaluated:
Oct 6, 2020
Accession:
VCV000206837.8
Variation ID:
206837
Description:
single nucleotide variant
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NM_001165963.4(SCN1A):c.4547C>A (p.Ser1516Ter)

Allele ID
201481
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q24.3
Genomic location
2: 165996047 (GRCh38) GRCh38 UCSC
2: 166852557 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_8:g.82593C>A
NC_000002.11:g.166852557G>T
NC_000002.12:g.165996047G>T
... more HGVS
Protein change
S1505*, S1516*, S1487*, S1504*, S702*, S1488*
Other names
p.S1516*:TCG>TAG
Canonical SPDI
NC_000002.12:165996046:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA317493
dbSNP: rs139300715
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Jul 17, 2019 RCV000188961.6
Pathogenic 3 criteria provided, multiple submitters, no conflicts Mar 23, 2018 RCV000416525.2
Pathogenic 1 criteria provided, single submitter Oct 31, 2018 RCV000763458.1
Pathogenic 1 criteria provided, single submitter Oct 6, 2020 RCV001050764.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SCN1A Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
1341 2698
LOC102724058 - - - GRCh38 - 1321

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jul 06, 2016)
criteria provided, single submitter
()
Method: clinical testing
Severe myoclonic epilepsy in infancy
Allele origin: de novo
Center of Genomic medicine, Geneva,University Hospital of Geneva
Accession: SCV000494451.1
Submitted: (Sep 13, 2016)
Evidence details
Pathogenic
(Mar 01, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000615037.2
Submitted: (Aug 31, 2018)
Evidence details
Publications
PubMed (8)
Pathogenic
(Jul 17, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000242592.14
Submitted: (Sep 24, 2021)
Evidence details
Comment:
Reported as a de novo variant in association with severe myoclonic epilepsy in infancy (SMEI) and Dravet syndrome (Sugawara et al., 2002; Mancardi et al., … (more)
Pathogenic
(Sep 01, 2017)
criteria provided, single submitter
Method: clinical testing
Severe myoclonic epilepsy in infancy
(Autosomal dominant inheritance)
Allele origin: de novo
Baylor Genetics
Accession: SCV000807531.1
Submitted: (Oct 16, 2017)
Evidence details
Publications
PubMed (2)
Comment:
This variant has been previously reported as disease-causing and was found once in our laboratory de novo in a 10-month-old female with afebrile seizures (onset … (more)
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Generalized epilepsy with febrile seizures plus, type 2
Severe myoclonic epilepsy in infancy
Familial hemiplegic migraine type 3
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894235.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Mar 23, 2018)
criteria provided, single submitter
Method: clinical testing
Severe myoclonic epilepsy in infancy
Allele origin: germline
Blueprint Genetics
Accession: SCV001426156.1
Submitted: (Jul 23, 2020)
Evidence details
Pathogenic
(Oct 06, 2020)
criteria provided, single submitter
Method: clinical testing
Early infantile epileptic encephalopathy with suppression bursts
Allele origin: germline
Invitae
Accession: SCV001214886.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change creates a premature translational stop signal (p.Ser1516*) in the SCN1A gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929587.1
Submitted: (Sep 23, 2021)
Evidence details
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
Human Genetics - Radboudumc,Radboudumc
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958735.1
Submitted: (Sep 30, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities. Zhang Y PloS one 2015 PMID: 26544041
Mitochondrial respiratory chain defects in skin fibroblasts from patients with Dravet syndrome. Doccini S Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2015 PMID: 26169758
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 Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Molecular findings among patients referred for clinical whole-exome sequencing. Yang Y JAMA 2014 PMID: 25326635
Early clinical features and diagnosis of Dravet syndrome in 138 Chinese patients with SCN1A mutations. Xu X Brain & development 2014 PMID: 24168886
De novo SCN1A mutations in Dravet syndrome and related epileptic encephalopathies are largely of paternal origin. Heron SE Journal of medical genetics 2010 PMID: 19589774
Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. Depienne C Journal of medical genetics 2009 PMID: 18930999
The spectrum of SCN1A-related infantile epileptic encephalopathies. Harkin LA Brain : a journal of neurology 2007 PMID: 17347258
Familial occurrence of febrile seizures and epilepsy in severe myoclonic epilepsy of infancy (SMEI) patients with SCN1A mutations. Mancardi MM Epilepsia 2006 PMID: 17054684
Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms. Wallace RH Neurology 2003 PMID: 14504318
Frequent mutations of SCN1A in severe myoclonic epilepsy in infancy. Sugawara T Neurology 2002 PMID: 11940708

Text-mined citations for rs139300715...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 08, 2021