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NM_001165963.4(SCN1A):c.4786C>T (p.Arg1596Cys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Nov 19, 2021)
Last evaluated:
Feb 26, 2020
Accession:
VCV000068553.13
Variation ID:
68553
Description:
single nucleotide variant
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NM_001165963.4(SCN1A):c.4786C>T (p.Arg1596Cys)

Allele ID
79445
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q24.3
Genomic location
2: 165994212 (GRCh38) GRCh38 UCSC
2: 166850722 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_8:g.84428C>T
LRG_8t1:c.4753C>T
NC_000002.11:g.166850722G>A
... more HGVS
Protein change
R1585C, R1596C, R1568C, R1584C, R1567C, R782C
Other names
p.R1596C:CGC>TGC
Canonical SPDI
NC_000002.12:165994211:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Links
ClinGen: CA145250
UniProtKB/Swiss-Prot: VAR_043368
dbSNP: rs121917993
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 Sep 19, 2018 RCV000188978.7
Pathogenic 1 criteria provided, single submitter Oct 29, 2018 RCV000794558.1
Likely pathogenic 1 criteria provided, single submitter Dec 11, 2019 RCV001031013.1
Pathogenic 1 criteria provided, single submitter Feb 26, 2020 RCV001253159.1
not provided 1 no assertion provided - RCV000059427.1
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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
1348 2705
LOC102724058 - - - GRCh38 - 1321

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Sep 29, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000615039.1
Submitted: (Aug 17, 2017)
Evidence details
Publications
PubMed (7)
Pathogenic
(Sep 19, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000242609.14
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R1596C missense variant in the SCN1A gene has been reported previously as a de novo pathogenic variant in association with Dravet syndrome and other … (more)
Pathogenic
(Oct 29, 2018)
criteria provided, single submitter
Method: clinical testing
Early infantile epileptic encephalopathy with suppression bursts
Allele origin: germline
Invitae
Accession: SCV000933973.1
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces arginine with cysteine at codon 1596 of the SCN1A protein (p.Arg1596Cys). The arginine residue is highly conserved and there is a … (more)
Likely pathogenic
(Dec 11, 2019)
criteria provided, single submitter
Method: research
Generalized epilepsy with febrile seizures plus, type 2
(Sporadic)
Allele origin: de novo
Cavalleri Lab, Royal College of Surgeons in Ireland
Accession: SCV001160806.1
Submitted: (Dec 11, 2019)
Evidence details
Publications
PubMed (1)
Comment:
ACMG evidence PS2, PP2, PP3
Pathogenic
(Feb 26, 2020)
criteria provided, single submitter
Method: clinical testing
Severe myoclonic epilepsy in infancy
Allele origin: germline
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001428734.1
Submitted: (Apr 20, 2020)
Evidence details
Comment:
This variant was identified as de novo (maternity and paternity confirmed).
Pathogenic
(Aug 01, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001245868.6
Submitted: (Jul 04, 2021)
Evidence details
Pathogenic
(Feb 28, 2020)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002020003.1
Submitted: (Nov 19, 2021)
Evidence details
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: unknown
UniProtKB/Swiss-Prot
Accession: SCV000090951.1
Submitted: (Apr 28, 2011)
Comment:
Patient phenotype: Cryptogenic focal epilepsy
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
A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability. Benson KA European journal of human genetics : EJHG 2020 PMID: 32238909
Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies. Møller RS Molecular syndromology 2016 PMID: 27781031
Pitfalls in genetic testing: the story of missed SCN1A mutations. Djémié T Molecular genetics & genomic medicine 2016 PMID: 27465585
From focal epilepsy to Dravet syndrome--Heterogeneity of the phenotype due to SCN1A mutations of the p.Arg1596 amino acid residue in the Nav1.1 subunit. Hoffman-Zacharska D Neurologia i neurochirurgia polska 2015 PMID: 26188943
Atypical multifocal Dravet syndrome lacks generalized seizures and may show later cognitive decline. Kim YO Developmental medicine and child neurology 2014 PMID: 24328833
Presence of epilepsy-associated variants in large exome databases. Cherepanova NS Journal of neurogenetics 2013 PMID: 23527921
Genotype-phenotype associations in SCN1A-related epilepsies. Zuberi SM Neurology 2011 PMID: 21248271
Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. Depienne C Journal of medical genetics 2009 PMID: 18930999
Novel de novo mutation of a conserved SCN1A amino-acid residue (R1596). Dlugos DJ Pediatric neurology 2007 PMID: 17903680
The spectrum of SCN1A-related infantile epileptic encephalopathies. Harkin LA Brain : a journal of neurology 2007 PMID: 17347258

Text-mined citations for rs121917993...

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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 Nov 28, 2021