NM_001365536.1(SCN9A):c.2720G>A (p.Arg907Gln) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Aug 4, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001208223.2

Allele description [Variation Report for NM_001365536.1(SCN9A):c.2720G>A (p.Arg907Gln)]

NM_001365536.1(SCN9A):c.2720G>A (p.Arg907Gln)

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.2720G>A (p.Arg907Gln)
HGVS:
  • NC_000002.12:g.166277137C>T
  • NG_012798.1:g.103851G>A
  • NM_001365536.1:c.2720G>AMANE SELECT
  • NM_002977.3:c.2687G>A
  • NP_001352465.1:p.Arg907Gln
  • NP_002968.1:p.Arg896Gln
  • LRG_369t1:c.2687G>A
  • LRG_369:g.103851G>A
  • LRG_369p1:p.Arg896Gln
  • NC_000002.11:g.167133647C>T
  • NR_110260.1:n.919C>T
Protein change:
R896Q
Links:
dbSNP: rs1024152367
NCBI 1000 Genomes Browser:
rs1024152367
Molecular consequence:
  • NM_001365536.1:c.2720G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002977.3:c.2687G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_110260.1:n.919C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Functional consequence:
loss_of_function_variant [Sequence Ontology: SO:0002054]

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001379600Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 4, 2019)
germlineclinical testing

PubMed (3)
[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

A novel SCN9A splicing mutation in a compound heterozygous girl with congenital insensitivity to pain, hyposmia and hypogeusia.

Marchi M, Provitera V, Nolano M, Romano M, Maccora S, D'Amato I, Salvi E, Gerrits M, Santoro L, Lauria G.

J Peripher Nerv Syst. 2018 Sep;23(3):202-206. doi: 10.1111/jns.12280. Epub 2018 Jul 23.

PubMed [citation]
PMID:
29978519
PMCID:
PMC6767138

Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations.

Cox JJ, Sheynin J, Shorer Z, Reimann F, Nicholas AK, Zubovic L, Baralle M, Wraige E, Manor E, Levy J, Woods CG, Parvari R.

Hum Mutat. 2010 Sep;31(9):E1670-86. doi: 10.1002/humu.21325.

PubMed [citation]
PMID:
20635406
PMCID:
PMC2966863
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001379600.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine with glutamine at codon 896 of the SCN9A protein (p.Arg896Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another SCN9A variant in individuals affected with congenital insensitivity to pain (CIP) (PMID: 20635406, 29978519). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant has been reported to affect SCN9A protein function (PMID: 20635406). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Jul 7, 2021

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