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NM_001365536.1(SCN9A):c.2576T>C (p.Ile859Thr)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Nov 19, 2021)
Last evaluated:
Dec 11, 2019
Accession:
VCV000006350.7
Variation ID:
6350
Description:
single nucleotide variant
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NM_001365536.1(SCN9A):c.2576T>C (p.Ile859Thr)

Allele ID
21389
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q24.3
Genomic location
2: 166277281 (GRCh38) GRCh38 UCSC
2: 167133791 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_369t1:c.2543T>C LRG_369p1:p.Ile848Thr
LRG_369:g.103707T>C
NC_000002.11:g.167133791A>G
... more HGVS
Protein change
I848T, I859T
Other names
-
Canonical SPDI
NC_000002.12:166277280:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA340545
OMIM: 603415.0002
dbSNP: rs80356474
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Dec 11, 2019 RCV001067998.2
SCN9A-related peripheral neuropathies associated with increased pain
Pathogenic 1 criteria provided, single submitter Mar 12, 2019 RCV001270748.1
Pathogenic 2 no assertion criteria provided Jan 14, 2020 RCV000006722.4
Likely pathogenic 1 no assertion criteria provided - RCV001004018.1
Pathogenic 1 no assertion criteria provided Mar 17, 2021 RCV001781194.1
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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
Pathogenic
(Mar 12, 2019)
criteria provided, single submitter
Method: clinical testing
SCN9A-related peripheral neuropathies associated with increased pain
Allele origin: unknown
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001451497.1
Submitted: (Dec 14, 2020)
Evidence details
Publications
PubMed (8)
Comment:
The SCN9A c.2543T>C (p.Ile848Thr) variant is a missense variant and has been reported in at least seven studies, in which it is found in a … (more)
Pathogenic
(Dec 11, 2019)
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: SCV001233085.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces isoleucine with threonine at codon 848 of the SCN9A protein (p.Ile848Thr). The isoleucine residue is highly conserved and there is a … (more)
Pathogenic
(Sep 22, 2004)
no assertion criteria provided
Method: literature only
ERYTHERMALGIA, PRIMARY
Allele origin: germline
OMIM
Accession: SCV000026913.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (2)
Pathogenic
(Jan 14, 2020)
no assertion criteria provided
Method: literature only
Primary erythromelalgia
Allele origin: germline
GeneReviews
Accession: SCV000040964.2
Submitted: (Mar 23, 2020)
Evidence details
Publications
PubMed (2)
BookShelf: NBK1163
Likely pathogenic
(-)
no assertion criteria provided
Method: research
Acute episodes of neuropathic symptoms
Abnormality of pain sensation
Allele origin: unknown
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV001162079.1
Submitted: (Sep 13, 2019)
Evidence details
Publications
PubMed (1)
Pathogenic
(Mar 17, 2021)
no assertion criteria provided
Method: clinical testing
not provided
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002020035.1
Submitted: (Nov 19, 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
Whole-genome sequencing of patients with rare diseases in a national health system. Turro E Nature 2020 PMID: 32581362
<i>SCN9A</i> Neuropathic Pain Syndromes Hisama FM - 2020 PMID: 20301342
Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile. McDonnell A Brain : a journal of neurology 2016 PMID: 26920677
Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7. Namer B Pain 2015 PMID: 25993546
Exonic mutations in SCN9A (NaV1.7) are found in a minority of patients with erythromelalgia. Zhang Z Scandinavian journal of pain 2014 PMID: 29911575
Treatment with carbamazepine and gabapentin of a patient with primary erythermalgia (erythromelalgia) identified to have a mutation in the SCN9A gene, encoding a voltage-gated sodium channel. Natkunarajah J Clinical and experimental dermatology 2009 PMID: 19549232
Primary erythermalgia as a sodium channelopathy: screening for SCN9A mutations: exclusion of a causal role of SCN10A and SCN11A. Drenth JP Archives of dermatology 2008 PMID: 18347287
SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels. Drenth JP The Journal of investigative dermatology 2005 PMID: 15955112
Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. Cummins TR The Journal of neuroscience : the official journal of the Society for Neuroscience 2004 PMID: 15385606
Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. Yang Y Journal of medical genetics 2004 PMID: 14985375

Text-mined citations for rs80356474...

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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