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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000555200.9

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_002977.4:c.184A>G
NP_001352465.1:p.Ile62Val
NP_002968.1:p.Ile62Val
NP_002968.1:p.Ile62Val
NP_002968.2:p.Ile62Val
LRG_369t1:c.184A>G
LRG_369:g.69415A>G
LRG_369p1:p.Ile62Val
NC_000002.11:g.167168083T>C
NM_002977.2:c.184A>G
NM_002977.3:c.184A>G
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_002977.4:c.184A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuropathy, hereditary sensory and autonomic, type 2A (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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000649284	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 27, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19763161, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000649284

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 27, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV000649284.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 62 of the SCN9A protein (p.Ile62Val). This variant is present in population databases (rs121908920, gnomAD 0.006%). This missense change has been observed in individual(s) with febrile seizures (PMID: 19763161). ClinVar contains an entry for this variant (Variation ID: 6368). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN9A protein function with a negative predictive value of 95%. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

ClinVar

Relating variation to medicine