U.S. flag

An official website of the United States government

NM_001349253.2(SCN11A):c.743G>A (p.Arg248His) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 19, 2021
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:
RCV001243550.4

Allele description

NM_001349253.2(SCN11A):c.743G>A (p.Arg248His)

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.743G>A (p.Arg248His)
HGVS:
  • NC_000003.12:g.38921225C>T
  • NG_033859.2:g.135762G>A
  • NM_001349253.2:c.743G>AMANE SELECT
  • NM_014139.3:c.743G>A
  • NP_001336182.1:p.Arg248His
  • NP_054858.2:p.Arg248His
  • NC_000003.11:g.38962716C>T
  • NM_014139.2:c.743G>A
Protein change:
R248H
Links:
dbSNP: rs777219461
NCBI 1000 Genomes Browser:
rs777219461
Molecular consequence:
  • NM_001349253.2:c.743G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014139.3:c.743G>A - 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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001416718Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 19, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001416718.4

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 968422). This variant has not been reported in the literature in individuals affected with SCN11A-related conditions. This variant is present in population databases (rs777219461, ExAC 0.006%). This sequence change replaces arginine with histidine at codon 248 of the SCN11A protein (p.Arg248His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine.

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

Last Updated: Mar 16, 2024