U.S. flag

An official website of the United States government

NM_000335.5(SCN5A):c.5347G>A (p.Glu1783Lys) AND Cardiac arrhythmia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 1, 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:
RCV003591625.1

Allele description [Variation Report for NM_000335.5(SCN5A):c.5347G>A (p.Glu1783Lys)]

NM_000335.5(SCN5A):c.5347G>A (p.Glu1783Lys)

Gene:
SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p22.2
Genomic location:
Preferred name:
NM_000335.5(SCN5A):c.5347G>A (p.Glu1783Lys)
Other names:
p.E1784K:GAG>AAG
HGVS:
  • NC_000003.12:g.38551022C>T
  • NG_008934.1:g.103651G>A
  • NM_000335.5:c.5347G>AMANE SELECT
  • NM_001099404.2:c.5350G>A
  • NM_001099405.2:c.5296G>A
  • NM_001160160.2:c.5251G>A
  • NM_001160161.2:c.5188G>A
  • NM_001354701.2:c.5293G>A
  • NM_198056.3:c.5350G>A
  • NP_000326.2:p.Glu1783Lys
  • NP_001092874.1:p.Glu1784Lys
  • NP_001092875.1:p.Glu1766Lys
  • NP_001153632.1:p.Glu1751Lys
  • NP_001153633.1:p.Glu1730Lys
  • NP_001341630.1:p.Glu1765Lys
  • NP_932173.1:p.Glu1784Lys
  • NP_932173.1:p.Glu1784Lys
  • LRG_289t1:c.5350G>A
  • LRG_289t3:c.5350G>A
  • LRG_289:g.103651G>A
  • LRG_289p1:p.Glu1784Lys
  • NC_000003.11:g.38592513C>T
  • NM_001099404.1:c.5350G>A
  • NM_001099404.2:c.5350G>A
  • NM_198056.2:c.5350G>A
  • Q14524:p.Glu1784Lys
Protein change:
E1730K; GLU1784LYS
Links:
UniProtKB: Q14524#VAR_008959; OMIM: 600163.0008; dbSNP: rs137854601
NCBI 1000 Genomes Browser:
rs137854601
Molecular consequence:
  • NM_000335.5:c.5347G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099404.2:c.5350G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001099405.2:c.5296G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160160.2:c.5251G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001160161.2:c.5188G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354701.2:c.5293G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198056.3:c.5350G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiac arrhythmia
Synonyms:
Cardiac rhythm disease
Identifiers:
EFO: EFO_0004269; MONDO: MONDO:0007263; MedGen: C0003811; Human Phenotype Ontology: HP:0011675

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
SCV004361604Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Sep 1, 2023) 		germlineclinical testing

PubMed (11)
[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

Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel.

Wei J, Wang DW, Alings M, Fish F, Wathen M, Roden DM, George AL Jr.

Circulation. 1999 Jun 22;99(24):3165-71.

PubMed [citation]
PMID:
10377081

The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.

Makita N, Behr E, Shimizu W, Horie M, Sunami A, Crotti L, Schulze-Bahr E, Fukuhara S, Mochizuki N, Makiyama T, Itoh H, Christiansen M, McKeown P, Miyamoto K, Kamakura S, Tsutsui H, Schwartz PJ, George AL Jr, Roden DM.

J Clin Invest. 2008 Jun;118(6):2219-29. doi: 10.1172/JCI34057.

PubMed [citation]
PMID:
18451998
PMCID:
PMC2350431
See all PubMed Citations (11)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004361604.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This missense variant replaces glutamate with lysine at codon 1784 of the SCN5A protein. This variant is found within the highly conserved C-terminal region (a.a. 1773-2016). Rare nontruncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome or Long QT syndrome (PMID: 32893267). Functional studies have shown that this variant causes a reduction in peak sodium currents, a negative shift of steady-state inactivation, and an increase in late sodium currents in transfected cells (PMID: 18451998, 24439875, 27381756). This variant has been reported in over two hundred individuals affected with Brugada syndrome, long QT syndrome, sinus node dysfunction, or cardiac conduction disease from various population (PMID: 10377081, 18451998, 20129283, 21321465, 27381756, 27566755, 33164571). This variant has been shown to segregate with disease in multiple families (PMID: 10377081, 18451998, 27381756). Some carriers have exhibited phenotypic characteristics of both Brugada syndrome and long QT syndrome (PMID: 18451998, 21321465, 27381756, 28781849). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: Nov 30, 2024