NM_001365536.1(SCN9A):c.2576T>C (p.Ile859Thr) AND SCN9A-related peripheral neuropathies associated with increased pain

Clinical significance:Pathogenic (Last evaluated: Mar 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001270748.1

Allele description [Variation Report for NM_001365536.1(SCN9A):c.2576T>C (p.Ile859Thr)]

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

Genes:
SCN1A-AS1:SCN1A and SCN9A antisense RNA 1 [Gene - HGNC]
SCN9A:sodium voltage-gated channel alpha subunit 9 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001365536.1(SCN9A):c.2576T>C (p.Ile859Thr)
HGVS:
  • NC_000002.12:g.166277281A>G
  • NG_012798.1:g.103707T>C
  • NM_001365536.1:c.2576T>CMANE SELECT
  • NM_002977.3:c.2543T>C
  • NP_001352465.1:p.Ile859Thr
  • NP_002968.1:p.Ile848Thr
  • LRG_369t1:c.2543T>C
  • LRG_369:g.103707T>C
  • LRG_369p1:p.Ile848Thr
  • NC_000002.11:g.167133791A>G
  • NM_002977.2:c.2543T>C
Protein change:
I848T; ILE848THR
Links:
OMIM: 603415.0002; dbSNP: rs80356474
NCBI 1000 Genomes Browser:
rs80356474
Molecular consequence:
  • NM_001365536.1:c.2576T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002977.3:c.2543T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
SCN9A-related peripheral neuropathies associated with increased pain
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001451497Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Pathogenic
(Mar 12, 2019)
unknownclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.

Yang Y, Wang Y, Li S, Xu Z, Li H, Ma L, Fan J, Bu D, Liu B, Fan Z, Wu G, Jin J, Ding B, Zhu X, Shen Y.

J Med Genet. 2004 Mar;41(3):171-4.

PubMed [citation]
PMID:
14985375
PMCID:
PMC1735695

Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy.

Cummins TR, Dib-Hajj SD, Waxman SG.

J Neurosci. 2004 Sep 22;24(38):8232-6.

PubMed [citation]
PMID:
15385606
PMCID:
PMC6729696
See all PubMed Citations (8)

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV001451497.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

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 heterozygous state in a total of 10 individuals with inherited erythromelalgia (Yang et al. 2004; Drenth et al. 2005; Drenth et al. 2008; Natkunarajah et al. 2009; Zhang et al. 2014; Namer et al. 2015; McDonnell et al. 2016). The age of onset was reported at three to five years in individuals carrying the p.Ile848Thr variant. In two families, the variant was shown to segregate with disease. The p.Ile848Thr variant was absent from 350 control subjects and is not found in the Genome Aggregation Database, in a region of good sequence coverage, so the variant is presumed to be rare. Functional studies in C-fibers from a patient carrying the p.Ile848Thr variant demonstrated an enhanced early subnormal conduction in the velocity recovery cycles (Namer et al. 2015). In addition, HEK293 cells expressing this variant exhibited altered sodium channel function compared to wild type (Cummins et al. 2004). Based on the collective evidence and application of the ACMG criteria, the p.Ile848Thr variant is classified as pathogenic for SCN9A-related peripheral neuropathies associated with increased pain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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