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NM_000334.4(SCN4A):c.3478A>G (p.Ile1160Val) AND Familial hyperkalemic periodic paralysis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 5, 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:
RCV003505082.2

Allele description [Variation Report for NM_000334.4(SCN4A):c.3478A>G (p.Ile1160Val)]

NM_000334.4(SCN4A):c.3478A>G (p.Ile1160Val)

Genes:
GH-LCR:growth hormone locus control region [Gene]
SCN4A:sodium voltage-gated channel alpha subunit 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q23.3
Genomic location:
Preferred name:
NM_000334.4(SCN4A):c.3478A>G (p.Ile1160Val)
HGVS:
  • NC_000017.11:g.63945602T>C
  • NG_011699.1:g.32317A>G
  • NG_042788.1:g.28510T>C
  • NM_000334.4:c.3478A>GMANE SELECT
  • NP_000325.4:p.Ile1160Val
  • NC_000017.10:g.62022962T>C
  • P35499:p.Ile1160Val
Protein change:
I1160V; ILE1160VAL
Links:
UniProtKB: P35499#VAR_017793; OMIM: 603967.0010; dbSNP: rs121908549
NCBI 1000 Genomes Browser:
rs121908549
Molecular consequence:
  • NM_000334.4:c.3478A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial hyperkalemic periodic paralysis
Synonyms:
Hyperkalemic periodic paralysis; Gamstorp episodic adynamy; Gamstorp disease
Identifiers:
MONDO: MONDO:0008224; MedGen: C0238357; Orphanet: 682; OMIM: 170500; Human Phenotype Ontology: HP:0007215

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004297511Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 5, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis.

Ptáĉek LJ, Tawil R, Griggs RC, Meola G, McManis P, Barohn RJ, Mendell JR, Harris C, Spitzer R, Santiago F, et al.

Neurology. 1994 Aug;44(8):1500-3.

PubMed [citation]
PMID:
8058156

The spectrum of myotonic and myopathic disorders in a pediatric electromyography laboratory over 12 years.

Shah DU, Darras BT, Markowitz JA, Jones HR Jr, Kang PB.

Pediatr Neurol. 2012 Aug;47(2):97-100. doi: 10.1016/j.pediatrneurol.2012.05.003.

PubMed [citation]
PMID:
22759684
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297511.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1160 of the SCN4A protein (p.Ile1160Val). This missense change has been observed in individuals with clinical features of myotonia congenita (PMID: 8058156, 22759684, 29606556; Invitae). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SCN4A function (PMID: 9336185). 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 expected to disrupt SCN4A protein function. ClinVar contains an entry for this variant (Variation ID: 5906).

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

Last Updated: Sep 29, 2024