NM_001365536.1(SCN9A):c.184A>G (p.Ile62Val) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Oct 16, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000555200.6

Allele description [Variation Report for NM_001365536.1(SCN9A):c.184A>G (p.Ile62Val)]

NM_001365536.1(SCN9A):c.184A>G (p.Ile62Val)

Gene:
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.184A>G (p.Ile62Val)
HGVS:
  • NC_000002.12:g.166311573T>C
  • NG_012798.1:g.69415A>G
  • NM_001365536.1:c.184A>GMANE SELECT
  • NM_002977.3:c.184A>G
  • NP_001352465.1:p.Ile62Val
  • NP_002968.1:p.Ile62Val
  • LRG_369t1:c.184A>G
  • LRG_369:g.69415A>G
  • LRG_369p1:p.Ile62Val
  • NC_000002.11:g.167168083T>C
  • Q15858:p.Ile62Val
Protein change:
I62V; ILE62VAL
Links:
UniProtKB: Q15858#VAR_064596; OMIM: 603415.0020; dbSNP: rs121908920
NCBI 1000 Genomes Browser:
rs121908920
Molecular consequence:
  • NM_001365536.1:c.184A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002977.3:c.184A>G - 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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000649284Invitaecriteria provided, single submitter
Uncertain significance
(Oct 16, 2020)
germlineclinical testing

PubMed (2)
[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 role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome.

Singh NA, Pappas C, Dahle EJ, Claes LR, Pruess TH, De Jonghe P, Thompson J, Dixon M, Gurnett C, Peiffer A, White HS, Filloux F, Leppert MF.

PLoS Genet. 2009 Sep;5(9):e1000649. doi: 10.1371/journal.pgen.1000649. Epub 2009 Sep 18.

PubMed [citation]
PMID:
19763161
PMCID:
PMC2730533

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000649284.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces isoleucine with valine at codon 62 of the SCN9A protein (p.Ile62Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs121908920, ExAC 0.009%). This variant has been observed in an individual affected with febrile seizures (PMID: 19763161). ClinVar contains an entry for this variant (Variation ID: 6368). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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