NM_001349253.2(SCN11A):c.1142T>C (p.Ile381Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 17, 2022
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:: RCV002512564.2

Allele description [Variation Report for NM_001349253.2(SCN11A):c.1142T>C (p.Ile381Thr)]

NM_001349253.2(SCN11A):c.1142T>C (p.Ile381Thr)

Gene:

SCN11A:sodium voltage-gated channel alpha subunit 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_001349253.2(SCN11A):c.1142T>C (p.Ile381Thr)

HGVS:

NC_000003.12:g.38909154A>G
NG_033859.2:g.147833T>C
NM_001349253.2:c.1142T>CMANE SELECT
NM_014139.3:c.1142T>C
NP_001336182.1:p.Ile381Thr
NP_054858.2:p.Ile381Thr
NC_000003.11:g.38950645A>G
NM_014139.2:c.1142T>C
Q9UI33:p.Ile381Thr

Protein change:

I381T; ILE381THR

Links:

UniProtKB: Q9UI33#VAR_076682; OMIM: 604385.0005; dbSNP: rs606231280

NCBI 1000 Genomes Browser:

rs606231280

Molecular consequence:

NM_001349253.2:c.1142T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014139.3:c.1142T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary sensory and autonomic neuropathy type 7
Synonyms:: HSAN VII; Neuropathy, hereditary sensory and autonomic, type VII
Identifiers:: MONDO: MONDO:0014244; MedGen: C3809882; Orphanet: 391397; OMIM: 615548

Name:: Familial episodic pain syndrome with predominantly lower limb involvement
Synonyms:: Episodic pain syndrome, familial, 3
Identifiers:: MONDO: MONDO:0014247; MedGen: C3809899; Orphanet: 391384; Orphanet: 391392; OMIM: 615552

Recent activity

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streptomycin/spectinomycin adenyltransferase [Binary vector with BdCESA7 promote...
streptomycin/spectinomycin adenyltransferase [Binary vector with BdCESA7 promoter]
gi|998429339|gb|AMK47886.1|

Protein
Microbe sample from Salmonella enterica subsp. enterica serovar Infantis
Microbe sample from Salmonella enterica subsp. enterica serovar Infantis

biosample
BioSample links for Nucleotide (Select 2711461161) (1)
BioSample
Taxonomy Links for BioSample (Select 3282367) (1)
Taxonomy
Rhinonycteridae rogdi-like protein (ROGDI) gene, partial cds.
Rhinonycteridae rogdi-like protein (ROGDI) gene, partial cds.
PopSet: 1914847981

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003262191	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24776970, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003262191

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 17, 2022)

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

Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy.

Huang J, Han C, Estacion M, Vasylyev D, Hoeijmakers JG, Gerrits MM, Tyrrell L, Lauria G, Faber CG, Dib-Hajj SD, Merkies IS, Waxman SG; PROPANE Study Group..

Brain. 2014 Jun;137(Pt 6):1627-42. doi: 10.1093/brain/awu079. Epub 2014 Apr 27.

PubMed [citation]

PMID:: 24776970

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, SCV003262191.2

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

Description

This variant is present in population databases (rs606231280, gnomAD 0.002%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 381 of the SCN11A protein (p.Ile381Thr). This missense change has been observed in individuals with SCN11A-related conditions (PMID: 24776970). 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. Experimental studies have shown that this missense change affects SCN11A function (PMID: 24776970). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). ClinVar contains an entry for this variant (Variation ID: 157600).

#	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: May 1, 2024

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