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

Clinical significance:Pathogenic (Last evaluated: Dec 11, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001067998.2

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:
Hereditary sensory and autonomic neuropathy type IIA (HSAN2A)
Synonyms:
ACROOSTEOLYSIS, GIACCAI TYPE; ACROOSTEOLYSIS, NEUROGENIC; HSAN IIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0024309; MedGen: C2752089; Orphanet: 970; OMIM: 201300
Name:
Generalized epilepsy with febrile seizures plus, type 7 (GEFSP7)
Synonyms:
GEFS+, TYPE 7
Identifiers:
MONDO: MONDO:0013470; MedGen: C2751778; Orphanet: 36387; OMIM: 613863

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001233085Invitaecriteria provided, single submitter
Pathogenic
(Dec 11, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot 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

Exonic mutations in SCN9A (NaV1.7) are found in a minority of patients with erythromelalgia.

Zhang Z, Schmelz M, Segerdahl M, Quiding H, Centerholt C, Juréus A, Carr TH, Whiteley J, Salter H, Kvernebo MS, Ørstavik K, Helås T, Kleggetveit IP, Lunden LK, Jørum E.

Scand J Pain. 2014 Oct 1;5(4):217-225. doi: 10.1016/j.sjpain.2014.09.002.

PubMed [citation]
PMID:
29911575
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001233085.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

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 moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal dominant primary erythromelalgia (PMID: 14985375, 29911575). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6350). This variant has been reported to affect SCN9A protein function (PMID: 15385606). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

Support Center