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NM_001365536.1(SCN9A):c.1555G>A (p.Glu519Lys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(5);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: Oct 1, 2021)
Last evaluated:
Apr 28, 2021
Accession:
VCV000193859.10
Variation ID:
193859
Description:
single nucleotide variant
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NM_001365536.1(SCN9A):c.1555G>A (p.Glu519Lys)

Allele ID
191022
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q24.3
Genomic location
2: 166286383 (GRCh38) GRCh38 UCSC
2: 167142893 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q15858:p.Glu519Lys
LRG_369t1:c.1555G>A LRG_369p1:p.Glu519Lys
LRG_369:g.94605G>A
... more HGVS
Protein change
E519K
Other names
-
Canonical SPDI
NC_000002.12:166286382:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00060 (T)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00063
Exome Aggregation Consortium (ExAC) 0.00043
The Genome Aggregation Database (gnomAD), exomes 0.00045
The Genome Aggregation Database (gnomAD) 0.00059
Trans-Omics for Precision Medicine (TOPMed) 0.00080
1000 Genomes Project 0.00060
The Genome Aggregation Database (gnomAD) 0.00061
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00091
Links
ClinGen: CA239538
UniProtKB: Q15858#VAR_064603
dbSNP: rs187453572
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Apr 28, 2021 RCV000723961.2
Likely benign 1 criteria provided, single submitter Jun 14, 2016 RCV000277449.2
Likely benign 1 criteria provided, single submitter Apr 28, 2017 RCV000290806.2
Likely benign 1 criteria provided, single submitter Apr 28, 2017 RCV000388718.2
Likely benign 1 criteria provided, single submitter Apr 28, 2017 RCV000348148.2
Likely benign 1 criteria provided, single submitter Nov 26, 2020 RCV000468717.7
Uncertain significance 1 criteria provided, single submitter Jul 11, 2019 RCV001332206.1
Uncertain significance 1 no assertion criteria provided Aug 25, 2017 RCV000781948.1
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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-AS1 - - - GRCh38 - 1176
SCN9A - - GRCh38
GRCh37
236 1439

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Sep 09, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000225304.5
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (1)
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(Jul 11, 2019)
criteria provided, single submitter
Method: clinical testing
Generalized epilepsy with febrile seizures plus, type 7
Allele origin: unknown
Baylor Genetics
Accession: SCV001524448.1
Submitted: (Feb 21, 2021)
Evidence details
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Likely benign
(Jun 14, 2016)
criteria provided, single submitter
Method: clinical testing
Small Fiber Neuropathy
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000418695.2
Submitted: (Oct 18, 2016)
Evidence details
Likely benign
(Apr 28, 2017)
criteria provided, single submitter
Method: clinical testing
Paroxysmal extreme pain disorder
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000418694.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(Apr 28, 2017)
criteria provided, single submitter
Method: clinical testing
Primary erythromelalgia
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000418699.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(Apr 28, 2017)
criteria provided, single submitter
Method: clinical testing
Indifference to pain, congenital, autosomal recessive
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000418698.3
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Likely benign
(Nov 26, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary sensory and autonomic neuropathy type IIA
Generalized epilepsy with febrile seizures plus, type 7
Allele origin: germline
Invitae
Accession: SCV000548352.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Apr 28, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000617190.2
Submitted: (Oct 01, 2021)
Evidence details
Comment:
Reported previously as a maternally inherited variant in a patient with Dravet syndrome; the clinical significance is uncertain (Singh et al., 2009). To our knowledge, … (more)
Uncertain significance
(Aug 25, 2017)
no assertion criteria provided
Method: clinical testing
Seizures
Allele origin: germline
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital
Accession: SCV000920392.1
Submitted: (Feb 28, 2019)
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
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. Singh NA PLoS genetics 2009 PMID: 19763161
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SCN9A - - - -

Text-mined citations for rs187453572...

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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 27, 2021