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NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met) AND SCN4A-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 26, 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:
RCV004532296.2

Allele description [Variation Report for NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met)]

NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met)

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.2111C>T (p.Thr704Met)
HGVS:
  • NC_000017.11:g.63957427G>A
  • NG_011699.1:g.20492C>T
  • NG_042788.1:g.40335G>A
  • NM_000334.4:c.2111C>TMANE SELECT
  • NP_000325.4:p.Thr704Met
  • NC_000017.10:g.62034787G>A
  • P35499:p.Thr704Met
Protein change:
T704M; THR704MET
Links:
UniProtKB: P35499#VAR_001562; OMIM: 603967.0001; dbSNP: rs80338957
NCBI 1000 Genomes Browser:
rs80338957
Molecular consequence:
  • NM_000334.4:c.2111C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
SCN4A-related disorder
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004119921PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jun 26, 2023) 		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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004119921.1

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

Description

The SCN4A c.2111C>T variant is predicted to result in the amino acid substitution p.Thr704Met. This variant has been reported in many individuals and families with hyperkalemic periodic paralysis and is one of the most common causative variants in SCN4A for this disorder (Ptácek et al 1991. PubMed ID: 1659948; Jurkat-Rott K et al 2007. PubMed ID: 17395131; Huang S et al 2019. PubMed ID: 30931713; Vereb N et al 2020. PubMed ID: 33263785 ). This variant was also reported in a large Turkish family with hypokalemic periodic paralysis (Gun Bilgic D et al 2020. PubMed ID: 32336642). The c.2111C>T variant has been reported to occur de novo in at least one individual with hyperkalemic periodic paralysis (Han JY et al 2011. PubMed ID: 22253644). Functional studies indicate this variant significantly impairs slow inactivation (Bendahhou S et al 1999. PubMed ID: 10366610). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.

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

Last Updated: Jan 19, 2025