Gene: SCN5A

Alternate names for this Gene: CDCD2|CMD1E|CMPD2|HB1|HB2|HBBD|HH1|ICCD|IVF|LQT3|Nav1.5|PFHB1|SSS1|VF1

Gene Summary: The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene are a cause of long QT syndrome type 3 (LQT3), an autosomal dominant cardiac disease. Alternative splicing results in several transcript variants encoding different isoforms.

Gene is located in Chromosome: 3

Location in Chromosome : 3p22.2

Description of this Gene: sodium voltage-gated channel alpha subunit 5

Type of Gene: protein-coding

rs137854617 in SCN5A gene and ATRIAL FIBRILLATION, FAMILIAL, 10 PMID 18088563 2008 Cardiac sodium channel mutation in atrial fibrillation.

PMID 18378609 2008 Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation.

rs137854618 in SCN5A gene and ATRIAL STANDSTILL 1 PMID 23420830 2013 MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome.

PMID 12522116 2003 A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill.

rs786205271 in SCN5A gene and Arthrogryposis PMID 31680123 2020 The genomic and clinical landscape of fetal akinesia.

rs7374540 in SCN5A gene and Atrial Fibrillation PMID 29892015 2018 Multi-ethnic genome-wide association study for atrial fibrillation.

PMID 30061737 2018 Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.

rs1060501135 in SCN5A gene and Brugada Syndrome (disorder) PMID 22789973 2012 Brugada syndrome 2012.

PMID 20129283 2010 An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

PMID 23872634 2013 Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.

PMID 19843921 2009 Exercise-induced ECG changes in Brugada syndrome.

PMID 26173111 2015 Comprehensive Genetic Characterization of a Spanish Brugada Syndrome Cohort.

PMID 29202755 2017 H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters.

PMID 17404158 2007 Clinical aspects and prognosis of Brugada syndrome in children.

PMID 20090423 2010 Impaired stretch modulation in potentially lethal cardiac sodium channel mutants.

PMID 9506831 1998 A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome.

PMID 10772658 2000 "A revised view of cardiac sodium channel ""blockade"" in the long-QT syndrome."

PMID 9495298 1998 Phenotypic characterization of a novel long-QT syndrome mutation (R1623Q) in the cardiac sodium channel.

PMID 19167409 2009 Differential modulation of late sodium current by protein kinase A in R1623Q mutant of LQT3.

PMID 15621041 2005 Intrinsic mechanism of the enhanced rate-dependent QT shortening in the R1623Q mutant of the LQT3 syndrome.

PMID 10618304 2000 Cardiac Na(+) channel dysfunction in Brugada syndrome is aggravated by beta(1)-subunit.

PMID 10961955 2000 The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge.

PMID 16379539 2005 Gene sequencing in neonates and infants with the long QT syndrome.

PMID 21321465 2011 Identification of six novel SCN5A mutations in Japanese patients with Brugada syndrome.

PMID 11901046 2002 Natural history of Brugada syndrome: insights for risk stratification and management.

PMID 18452873 2008 Prevalence of early-onset atrial fibrillation in congenital long QT syndrome.

PMID 10973849 2000 Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

PMID 10377081 1999 Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel.

PMID 25348405 2015 UniProt: a hub for protein information.

PMID 12877697 2003 Catecholamine-provoked microvoltage T wave alternans in genotyped long QT syndrome.

PMID 23631430 2013 Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory.

PMID 24871449 2014 High prevalence of the SCN5A E1784K mutation in school children with long QT syndrome living on the Okinawa islands.

PMID 18451998 2008 Of 41 E1784K carriers, 93% had LQT3, 22% had BrS, and 39% had sinus node dysfunction.

PMID 15840476 2005 Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

PMID 10727653 2000 Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes.

PMID 24762805 2014 Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics.

PMID 19841300 2009 Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.

PMID 14961552 2003 Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease.

PMID 19026623 2009 Rapid, sensitive and inexpensive detection of SCN5A genetic variations by high resolution melting analysis.

PMID 10940383 2000 A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome.

PMID 23139254 2012 Integration of genetics into a systems model of electrocardiographic traits using HumanCVD BeadChip.

PMID 25326637 2014 Clinical exome sequencing for genetic identification of rare Mendelian disorders.

PMID 26798387 2016 Genetic Variation of SCN5A in Korean Patients with Sick Sinus Syndrome.

PMID 22247482 2012 A connexin40 mutation associated with a malignant variant of progressive familial heart block type I.

PMID 22581936 2012 Clinical application of exome sequencing in undiagnosed genetic conditions.

PMID 23195492 2012 Prevalence of SCN1A mutations in children with suspected Dravet syndrome and intractable childhood epilepsy.

PMID 11804990 2002 Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block.

PMID 17561957 2007 Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities.

PMID 22581653 2012 Paralogous annotation of disease-causing variants in long QT syndrome genes.

PMID 26283144 2015 Direct Measurement of Cardiac Na+ Channel Conformations Reveals Molecular Pathologies of Inherited Mutations.

PMID 17697823 2007 Comparison of long-term follow-up of electrocardiographic features in Brugada syndrome between the SCN5A-positive probands and the SCN5A-negative probands.

PMID 11823453 2002 Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome.

PMID 16254012 2006 Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique.

PMID 18929331 2008 A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation.

PMID 11410597 2001 We report the analysis of two novel mutations on the same codon, Y1795C (LQT-3) and Y1795H (BrS), expressed in HEK 293 cells and characterized using whole-cell patch clamp procedures.

PMID 14990510 2004 Structural effects of an LQT-3 mutation on heart Na+ channel gating.

PMID 12522116 2003 A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill.

PMID 21824921 2011 Striking In vivo phenotype of a disease-associated human SCN5A mutation producing minimal changes in vitro.

PMID 26111534 2015 Loss-of-Function SCN5A Mutations Associated With Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture.

PMID 23791817 2013 A transgenic zebrafish model of a human cardiac sodium channel mutation exhibits bradycardia, conduction-system abnormalities and early death.

PMID 24136861 2014 Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia.

PMID 21596231 2011 SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism.

PMID 15890323 2005 Brugada syndrome and fever: genetic and molecular characterization of patients carrying SCN5A mutations.

PMID 16643399 2006 Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation.

PMID 19251209 2009 Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies.

PMID 20031634 2009 SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome.

PMID 12106943 2002 Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients.

PMID 19862833 2009 The genetic basis of long QT and short QT syndromes: a mutation update.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

PMID 24363796 2013 Functional characterization of a novel frameshift mutation in the C-terminus of the Nav1.5 channel underlying a Brugada syndrome with variable expression in a Spanish family.

PMID 18551308 2008 Heterozygous nonsense SCN5A mutation W822X explains a simultaneous sudden infant death syndrome.

PMID 16239976 2005 A novel nonsense mutation in the SCN5A gene leads to Brugada syndrome and a silent gene mutation carrier state.

PMID 22899775 2012 Parental electrocardiographic screening identifies a high degree of inheritance for congenital and childhood nonimmune isolated atrioventricular block.

PMID 22370247 2012 Genetic variants in SCN5A promoter are associated with arrhythmia phenotype severity in patients with heterozygous loss-of-function mutation.

PMID 15671429 2005 Sodium channel mutations and susceptibility to heart failure and atrial fibrillation.

PMID 9521325 1998 Genetic basis and molecular mechanism for idiopathic ventricular fibrillation.

PMID 22739120 2012 Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Na(v)1.5 α-subunits.

PMID 24529773 2014 Three SCN5A mutations (V95I, R121Q, and R367H) have been previously implicated in BrS.

PMID 21273195 2011 Facilitatory and inhibitory effects of SCN5A mutations on atrial fibrillation in Brugada syndrome.

PMID 28341588 2017 Targeted Next-Generation Sequencing of 51 Genes Involved in Primary Electrical Disease.

PMID 28600387 2017 Genetic Testing in the Evaluation of Unexplained Cardiac Arrest: From the CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry).

PMID 27930701 2016 Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.

PMID 25194972 2014 Cardiac evaluation of pediatric relatives in sudden arrhythmic death syndrome: a 2-center experience.

PMID 18378609 2008 Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation.

PMID 21840964 2011 A novel strategy using cardiac sodium channel polymorphic fragments to rescue trafficking-deficient SCN5A mutations.

PMID 15851228 2004 A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family.

PMID 24295898 2014 Genetic analysis in a family affected by sick sinus syndrome may reduce the sudden death risk in a young aspiring competitive athlete.

PMID 23671135 2013 Sudden cardiac death with autopsy findings of uncertain significance: potential for erroneous interpretation.

PMID 16344400 2005 Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome.

PMID 28341781 2017 Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.

PMID 12693506 2003 Novel brugada SCN5A mutation leading to ST segment elevation in the inferior or the right precordial leads.

PMID 25650408 2015 Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome.

PMID 24815523 2014 Novel SCN5A mutation in amiodarone-responsive multifocal ventricular ectopy-associated cardiomyopathy.

PMID 25179549 2014 Targeted analysis of whole genome sequence data to diagnose genetic cardiomyopathy.

PMID 26733869 2015 Mutations in the Voltage Sensors of Domains I and II of Nav1.5 that are Associated with Arrhythmias and Dilated Cardiomyopathy Generate Gating Pore Currents.

PMID 18048769 2008 Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia.

PMID 25904541 2015 Enhanced Classification of Brugada Syndrome-Associated and Long-QT Syndrome-Associated Genetic Variants in the SCN5A-Encoded Na(v)1.5 Cardiac Sodium Channel.

PMID 22373669 2012 Mortality of inherited arrhythmia syndromes: insight into their natural history.

PMID 23414114 2013 High prevalence of genetic variants previously associated with Brugada syndrome in new exome data.

PMID 24951569 2014 The Brugada ECG and schizophrenia.

PMID 24573164 2014 Brugada syndrome disease phenotype explained in apparently benign sodium channel mutations.

PMID 17854786 2007 Here, we report the functional consequences of a novel missense SCN5A mutation, G1319V, identified in a BrS patient.

PMID 16039271 2005 Substitution of a conserved alanine in the domain IIIS4-S5 linker of the cardiac sodium channel causes long QT syndrome.

PMID 17698727 2007 Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients.

PMID 24721456 2014 A comprehensive electrocardiographic, molecular, and echocardiographic study of Brugada syndrome: validation of the 2013 diagnostic criteria.

PMID 11029409 2000 The biophysical properties of the SCN5A mutation T1620M associated with Brugada syndrome were examined for defects in intermediate inactivation (I:(M)), a gating process in Na(+) channels with kinetic features intermediate between fast and slow inactivation.

PMID 11123251 2001 Accelerated inactivation in a mutant Na(+) channel associated with idiopathic ventricular fibrillation.

PMID 10532948 1999 Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent.

PMID 23785128 2013 Targeted sequence capture and GS-FLX Titanium sequencing of 23 hypertrophic and dilated cardiomyopathy genes: implementation into diagnostics.

PMID 11827685 2002 A mutant cardiac sodium channel with multiple biophysical defects associated with overlapping clinical features of Brugada syndrome and cardiac conduction disease.

PMID 15520322 2004 Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations.

PMID 17897635 2007 A novel C-terminal truncation SCN5A mutation from a patient with sick sinus syndrome, conduction disorder and ventricular tachycardia.

PMID 18361072 2008 A novel SCN5A deletion mutation in a child with ventricular tachycardia, recurrent aborted sudden death, and Brugada electrocardiographic pattern.

PMID 25829473 2016 The proband had a baseline electrocardiogram that showed Type 2 BrS changes, which escalated to a characteristic Type I BrS pattern during a treadmill test before polymorphic ventricular tachycardia onset at a cycle length of 250 ms. Mutational analysis across all 29 exons in SCN5A of the proband and first-degree relatives of the family revealed that the proband inherited a compound heterozygote mutation in SCN5A, specifically p.A226V and p.R1629X from each parent.

PMID 23420830 2013 MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome.

PMID 12639704 2003 Nucleotide changes in the translated region of SCN5A from Japanese patients with Brugada syndrome and control subjects.

PMID 22984773 2013 A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome.

PMID 15023552 2004 A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs.

PMID 17088455 2006 Genotype-specific onset of arrhythmias in congenital long-QT syndrome: possible therapy implications.

PMID 12566525 2003 The use of genotype-phenotype correlations in mutation analysis for the long QT syndrome.

PMID 17905336 2007 Long QT and Brugada syndrome gene mutations in New Zealand.

PMID 12209021 2002 A novel SCN5A mutation associated with long QT-3: altered inactivation kinetics and channel dysfunction.

PMID 21350584 2011 Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome.

PMID 12650885 2003 A novel LQT3 mutation implicates the human cardiac sodium channel domain IVS6 in inactivation kinetics.

PMID 22739120 2012 We aimed to characterize two BrS N-terminal mutations, R104W and R121W, a construct where this region was deleted, ΔNter, and a construct where only this region was present, Nter.

PMID 19606473 2009 The genetic basis of Brugada syndrome: a mutation update.

PMID 24529773 2014 Is sudden unexplained nocturnal death syndrome in Southern China a cardiac sodium channel dysfunction disorder?

PMID 20395683 2010 Sick sinus syndrome, progressive cardiac conduction disease, atrial flutter and ventricular tachycardia caused by a novel SCN5A mutation.

PMID 16325048 2005 High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations.

PMID 8917568 1996 Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome.

PMID 8620612 1996 Multiple mechanisms of Na+ channel--linked long-QT syndrome.

PMID 8541846 1995 Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia.

PMID 14753626 2003 The implications of genetic mutations in the sodium channel gene (SCN5A).

PMID 24529773 2014 Three SCN5A mutations (V95I, R121Q, and R367H) have been previously implicated in BrS.

PMID 22028457 2011 Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization.

PMID 19716085 2009 Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

PMID 21483645 2011 Rare variant mutations identified in pediatric patients with dilated cardiomyopathy.

PMID 25741286 2015 Cellular hyper-excitability caused by mutations that alter the activation process of voltage-gated sodium channels.

PMID 22710484 2012 Escape capture bigeminy: phenotypic marker of cardiac sodium channel voltage sensor mutation R222Q.

PMID 22999724 2012 R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy.

PMID 25210054 2014 Gain-of-function mutation of the SCN5A gene causes exercise-induced polymorphic ventricular arrhythmias.

PMID 22766342 2012 Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy.

PMID 25624448 2015 Gating pore currents are defects in common with two Nav1.5 mutations in patients with mixed arrhythmias and dilated cardiomyopathy.

PMID 22717692 2012 Identification of a strong genetic background for progressive cardiac conduction defect by epidemiological approach.

PMID 10471492 1999 Cardiac conduction defects associate with mutations in SCN5A.

PMID 21193062 2011 A novel mechanism for LQT3 with 2:1 block: a pore-lining mutation in Nav1.5 significantly affects voltage-dependence of activation.

PMID 22090166 2012 Brugada-like syndrome in infancy presenting with rapid ventricular tachycardia and intraventricular conduction delay.

PMID 22529811 2012 Our aim was to functionally characterize two novel Na(v)1.5 mutations (A124D and V1378M) in BrS patients.

PMID 28782696 2017 Heritability in a SCN5A-mutation founder population with increased female susceptibility to non-nocturnal ventricular tachyarrhythmia and sudden cardiac death.

PMID 22840528 2012 Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing.

PMID 17081365 2006 [Novel SCN5A gene mutations associated with Brugada syndrome: V95I, A1649V and delF1617].

PMID 20448214 2010 Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaking in sick sinus syndrome.

PMID 15665061 2005 Reduced voltage dependence of inactivation in the SCN5A sodium channel mutation delF1617.

PMID 14523039 2003 Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A).

PMID 24388587 2014 Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort.

PMID 23936059 2013 Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations.

PMID 23538271 2013 We describe a family showing the association between Brugada syndrome and epilepsy in which a known mutation in the SCN5A gene (p.W1095X, c.3284G>A) was identified.

PMID 24606995 2014 Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p.F29L in KCNH2.

PMID 27287068 2016 However, the SCN5A variants R568H and A993T can be classified as pathogenic LQTS3 causing mutations, while R222stop and R2012H are novel BrS causing mutations.

PMID 26467377 2016 p.Gln1507-Lys1508-Pro1509del mutation, p.Arg222Ter nonsense mutation, and p.Met1498Arg in LQTS, BrS, and SSS, respectively, are reported for the first time in the Iranian population.

PMID 22885917 2012 The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children.

PMID 26392562 2015 SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia.

PMID 29247119 2017 Applying High-Resolution Variant Classification to Cardiac Arrhythmogenic Gene Testing in a Demographically Diverse Cohort of Sudden Unexplained Deaths.

PMID 24631775 2014 Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths.

PMID 24895455 2014 PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5 channel expression and function.

PMID 15057319 2004 Loss of function associated with novel mutations of the SCN5A gene in patients with Brugada syndrome.

PMID 23276942 2013 Biomarker discovery by plasma proteomics in familial Brugada Syndrome.

PMID 19808440 2009 Absence of pathognomonic or inflammatory patterns in cardiac biopsies from patients with Brugada syndrome.

PMID 23840796 2013 A heterozygous deletion mutation in the cardiac sodium channel gene SCN5A with loss- and gain-of-function characteristics manifests as isolated conduction disease, without signs of Brugada or long QT syndrome.

PMID 26304136 2015 Familial Paralysis of the Atrium Due to a Mutation in SCN5A.

PMID 22675453 2012 A proton leak current through the cardiac sodium channel is linked to mixed arrhythmia and the dilated cardiomyopathy phenotype.

PMID 15863661 2005 Unconventional intronic splice site mutation in SCN5A associates with cardiac sodium channelopathy.

PMID 15808832 2005 Cryptic 5' splice site activation in SCN5A associated with Brugada syndrome.

rs1060499900 in SCN5A gene and Brugada Syndrome 1 PMID 23994779 2013 Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.

PMID 26776555 2016 SCN5A(K817E), a novel Brugada syndrome-associated mutation that alters the activation gating of NaV1.5 channel.

PMID 24167619 2013 Electrophysiological characteristics of a SCN5A voltage sensors mutation R1629Q associated with Brugada syndrome.

PMID 16266370 2005 Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac Na+ channel does not affect ion selectivity properties.

PMID 26279430 2015 De Novo Mutation in the SCN5A Gene Associated with Brugada Syndrome.

PMID 17081365 2006 [Novel SCN5A gene mutations associated with Brugada syndrome: V95I, A1649V and delF1617].

PMID 9521325 1998 Genetic basis and molecular mechanism for idiopathic ventricular fibrillation.

PMID 18456723 2008 Subepicardial phase 0 block and discontinuous transmural conduction underlie right precordial ST-segment elevation by a SCN5A loss-of-function mutation.

PMID 18451998 2008 The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.

PMID 16616735 2006 A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation.

PMID 18252757 2008 Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome.

PMID 18341814 2007 [Gene (SCN5A) mutation analysis of a Chinese family with Brugada syndrome].

PMID 17198989 2007 A sodium channel pore mutation causing Brugada syndrome.

PMID 19251209 2009 Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies.

PMID 16325048 2005 High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations.

PMID 10690282 1999 Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome.

PMID 10532948 1999 Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent.

PMID 11823453 2002 Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome.

PMID 12106943 2002 Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients.

PMID 19272188 2009 Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations.

PMID 15579534 2004 Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes.

PMID 21810866 2011 HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).

PMID 23788249 2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

PMID 27854360 2017 Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

PMID 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 26111534 2015 Loss-of-Function SCN5A Mutations Associated With Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture.

PMID 20129283 2010 An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

PMID 11807557 2002 A calcium sensor in the sodium channel modulates cardiac excitability.

PMID 21273195 2011 Facilitatory and inhibitory effects of SCN5A mutations on atrial fibrillation in Brugada syndrome.

PMID 15808832 2005 Cryptic 5' splice site activation in SCN5A associated with Brugada syndrome.

PMID 15863661 2005 Unconventional intronic splice site mutation in SCN5A associates with cardiac sodium channelopathy.

rs137854618 in SCN5A gene and CARDIOMYOPATHY, DILATED, 1E PMID 23420830 2013 MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome.

PMID 15466643 2004 SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia.

rs199473161 in SCN5A gene and Cardiomyopathy, Dilated PMID 24815523 2014 Novel SCN5A mutation in amiodarone-responsive multifocal ventricular ectopy-associated cardiomyopathy.

PMID 18048769 2008 Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia.

PMID 17442746 2007 Homozygous SCN5A mutation in Brugada syndrome with monomorphic ventricular tachycardia and structural heart abnormalities.

PMID 15671429 2005 Sodium channel mutations and susceptibility to heart failure and atrial fibrillation.

PMID 19412328 2008 Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy.

PMID 22766342 2012 Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy.

PMID 21167004 2010 SCN5A rare variants in familial dilated cardiomyopathy decrease peak sodium current depending on the common polymorphism H558R and common splice variant Q1077del.

PMID 19716085 2009 Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

PMID 22999724 2012 R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy.

PMID 22277643 2012 Criteria to predict carriers of a novel SCN5A mutation in a large Portuguese family affected by the Brugada syndrome.

PMID 21596231 2011 SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism.

PMID 20458009 2010 Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy.

PMID 22710484 2012 Escape capture bigeminy: phenotypic marker of cardiac sodium channel voltage sensor mutation R222Q.

PMID 20129283 2010 An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

PMID 9521325 1998 Genetic basis and molecular mechanism for idiopathic ventricular fibrillation.

PMID 22899775 2012 Parental electrocardiographic screening identifies a high degree of inheritance for congenital and childhood nonimmune isolated atrioventricular block.

rs137854601 in SCN5A gene and Congenital long QT syndrome PMID 24871449 2014 High prevalence of the SCN5A E1784K mutation in school children with long QT syndrome living on the Okinawa islands.

PMID 21321465 2011 Identification of six novel SCN5A mutations in Japanese patients with Brugada syndrome.

PMID 18451998 2008 The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.

PMID 11901046 2002 Natural history of Brugada syndrome: insights for risk stratification and management.

PMID 16379539 2005 Gene sequencing in neonates and infants with the long QT syndrome.

PMID 10727653 2000 Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes.

PMID 10377081 1999 Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel.

PMID 23631430 2013 Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory.

rs12720452 in SCN5A gene and Death in early adulthood PMID 27435932 2016 Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young.

rs12720452 in SCN5A gene and Death in infancy PMID 27435932 2016 Postmortem genetic screening for the identification, verification, and reporting of genetic variants contributing to the sudden death of the young.

rs786205271 in SCN5A gene and Early severe fetal akinesia sequence PMID 31680123 2020 The genomic and clinical landscape of fetal akinesia.

rs11708996 in SCN5A gene and Electrocardiogram: P-R interval PMID 30046033 2018 PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 20062060 2010 Genome-wide association study of PR interval.

PMID 20062063 2010 Several common variants modulate heart rate, PR interval and QRS duration.

PMID 21347284 2011 Genome-wide association studies of the PR interval in African Americans.

PMID 29127183 2018 Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at ID2.

PMID 23139255 2012 Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.

rs7638275 in SCN5A gene and Electrocardiography PMID 29622589 2018 Genome-Wide Associations of Global Electrical Heterogeneity ECG Phenotype: The ARIC (Atherosclerosis Risk in Communities) Study and CHS (Cardiovascular Health Study).

rs11708996 in SCN5A gene and Heart Function Tests PMID 21076409 2010 Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.

rs137854606 in SCN5A gene and Hereditary bundle branch system defect PMID 12574143 2003 Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system.

PMID 19251209 2009 Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies.

PMID 11234013 2001 A sodium-channel mutation causes isolated cardiac conduction disease.

PMID 11804990 2002 Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block.

PMID 23420830 2013 MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome.

PMID 12569159 2003 A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation.

PMID 23994779 2013 Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.

rs137854600 in SCN5A gene and LONG QT SYNDROME 3 PMID 15840476 2005 Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

PMID 12209021 2002 A novel SCN5A mutation associated with long QT-3: altered inactivation kinetics and channel dysfunction.

PMID 12454206 2003 A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation.

PMID 11410597 2001 Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes.

PMID 10627139 1998 Identification of a new SCN5A mutation, D1840G, associated with the long QT syndrome. Mutations in brief no. 153. Online.

PMID 11304498 2001 Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in the cardiac Na(+) channel.

PMID 10377081 1999 Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel.

PMID 10508990 1999 Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations.

PMID 10911008 2000 A molecular link between the sudden infant death syndrome and the long-QT syndrome.

PMID 9686753 1998 Novel LQT-3 mutation affects Na+ channel activity through interactions between alpha- and beta1-subunits.

PMID 16922724 2006 Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.

PMID 19716085 2009 Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

PMID 9506831 1998 Here we characterized a de novo missense mutation (R1623Q, S4 segment of domain 4) identified in an infant Japanese girl with a severe form of LQT3.

PMID 18451998 2008 The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.

PMID 18929331 2008 A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation.

PMID 21810866 2011 HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).

PMID 16414944 2005 Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.

PMID 26392562 2015 SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia.

PMID 18060054 2007 A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic response.

PMID 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 7651517 1995 Molecular mechanism for an inherited cardiac arrhythmia.

PMID 23788249 2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

PMID 27854360 2017 Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

PMID 8541846 1995 Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia.

PMID 18451998 2008 Heterologously expressed E1784K channels showed a 15.0-mV negative shift in the voltage dependence of Na channel inactivation and a 7.5-fold increase in flecainide affinity for resting-state channels, properties also seen with other LQT3 mutations associated with a mixed clinical phenotype.

PMID 24871449 2014 High prevalence of the SCN5A E1784K mutation in school children with long QT syndrome living on the Okinawa islands.

PMID 21321465 2011 Identification of six novel SCN5A mutations in Japanese patients with Brugada syndrome.

PMID 24784157 2014 The implications of familial incidental findings from exome sequencing: the NIH Undiagnosed Diseases Program experience.

PMID 10727653 2000 Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes.

PMID 9506831 1998 A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome.

PMID 14523039 2003 Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A).

PMID 20539757 2010 Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome.

PMID 16325048 2005 High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations.

PMID 15840483 2005 Novel Brugada SCN5A mutation causing sudden death in children.

PMID 12209021 2002 Here we describe a novel LQT-3 mutation I1768V (I1768V) located in the sixth transmembrane spanning segment of domain IV.

PMID 17210841 2007 Cardiac sodium channel dysfunction in sudden infant death syndrome.

PMID 17646591 2007 "Letter by O'Rourke regarding articles, ""Prevalence of long-QT syndrome gene variants in sudden infant death syndrome,"" ""Cardiac sodium channel dysfunction in sudden infant death syndrome,"" and ""Contribution of long-QT syndrome genes to sudden infant death syndrome: is it time to consider newborn electrocardiographic screening?""."

PMID 18451998 2008 Furthermore, these properties were absent in Na channels harboring the T1304M mutation, which is associated with LQT3 without a mixed clinical phenotype.

PMID 22685113 2012 High prevalence of long QT syndrome-associated SCN5A variants in patients with early-onset lone atrial fibrillation.

PMID 22378279 2012 High prevalence of genetic variants previously associated with LQT syndrome in new exome data.

PMID 10973849 2000 Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

PMID 19841300 2009 Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.

PMID 27041150 2016 KCNQ1 mutations associated with Jervell and Lange-Nielsen syndrome and autosomal recessive Romano-Ward syndrome in India-expanding the spectrum of long QT syndrome type 1.

PMID 15665061 2005 Reduced voltage dependence of inactivation in the SCN5A sodium channel mutation delF1617.

rs749697698 in SCN5A gene and Long QT Syndrome PMID 10973849 2000 Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.

PMID 17081365 2006 [Novel SCN5A gene mutations associated with Brugada syndrome: V95I, A1649V and delF1617].

PMID 19716085 2009 Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.

rs1553706324 in SCN5A gene and Multiple congenital anomalies PMID 15840476 2005 Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

PMID 9753711 1998 Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group.

PMID 22999724 2012 R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy.

PMID 10940383 2000 A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome.

PMID 18378609 2008 Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation.

PMID 22766342 2012 Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy.

PMID 16684018 2006 SCN5A mutation associated with cardiac conduction defect and atrial arrhythmias.

PMID 10471492 1999 Cardiac conduction defects associate with mutations in SCN5A.

PMID 17210839 2007 Prevalence of long-QT syndrome gene variants in sudden infant death syndrome.

PMID 16453024 2006 A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y.

PMID 25274057 2014 Genetic and clinical advances in congenital long QT syndrome.

PMID 15655131 2005 Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association.

PMID 14523039 2003 Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A).

PMID 19251209 2009 Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies.

PMID 20100972 2010 Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry.

PMID 11710892 2001 Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome.

PMID 20129283 2010 An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.

PMID 12736279 2003 Risk stratification in the long-QT syndrome.

PMID 22840528 2012 Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing: implications for genetic testing.

rs3922844 in SCN5A gene and P wave duration (observable entity) PMID 28794112 2017 Fifteen Genetic Loci Associated With the Electrocardiographic P Wave.

rs11708996 in SCN5A gene and QRS complex feature PMID 27659466 2016 52 Genetic Loci Influencing Myocardial Mass.

rs11129795 in SCN5A gene and QT interval feature (observable entity) PMID 19305409 2009 Common variants at ten loci modulate the QT interval duration in the QTSCD Study.

PMID 24952745 2014 Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 19305408 2009 Common variants at ten loci influence QT interval duration in the QTGEN Study.

PMID 29213071 2017 GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals.

rs41312411 in SCN5A gene and RESTING HEART RATE PMID 27798624 2016 Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality.

rs137854601 in SCN5A gene and Romano-Ward Syndrome PMID 10727653 2000 Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes.

PMID 21321465 2011 Identification of six novel SCN5A mutations in Japanese patients with Brugada syndrome.

PMID 10377081 1999 Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel.

PMID 15840476 2005 Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.

PMID 18508782 2008 Sudden arrhythmic death syndrome: familial evaluation identifies inheritable heart disease in the majority of families.

PMID 20564468 2010 A homozygous SCN5A mutation in a severe, recessive type of cardiac conduction disease.

rs137854611 in SCN5A gene and SICK SINUS SYNDROME 1, AUTOSOMAL RECESSIVE PMID 11748104 2001 Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family.

PMID 14523039 2003 Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A).

PMID 22795782 2012 [Cardiac sinus node dysfunction due to a new mutation of the SCN5A gene].

rs199473190 in SCN5A gene and Sudden infant death syndrome PMID 21810866 2011 HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).

PMID 19302788 2009 Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS infant linked to long QT syndrome.

PMID 18596570 2008 We studied three major genes causing long QT syndrome in 42 Japanese SIDS victims and found five mutations, KCNQ1-K598R, KCNH2-T895M, SCN5A-F532C, SCN5A-G1084S, and SCN5A-F1705S, in four cases; one case had both KCNH2-T895M and SCN5A-G1084S.

PMID 18596570 2008 We studied three major genes causing long QT syndrome in 42 Japanese SIDS victims and found five mutations, KCNQ1-K598R, KCNH2-T895M, SCN5A-F532C, SCN5A-G1084S, and SCN5A-F1705S, in four cases; one case had both KCNH2-T895M and SCN5A-G1084S.

PMID 19302788 2009 The correlation between the biophysical data and arrhythmia susceptibility suggested that the SIDS was secondary to the LQT3-associated S1333Y mutation.

PMID 18596570 2008 Cardiac ion channel gene mutations in sudden infant death syndrome.

PMID 18596570 2008 We studied three major genes causing long QT syndrome in 42 Japanese SIDS victims and found five mutations, KCNQ1-K598R, KCNH2-T895M, SCN5A-F532C, SCN5A-G1084S, and SCN5A-F1705S, in four cases; one case had both KCNH2-T895M and SCN5A-G1084S.

rs137854604 in SCN5A gene and Ventricular Fibrillation, Paroxysmal Familial, 1 PMID 10940383 2000 We performed genetic screenings of Japanese IVF patients and found a novel SCN5A missense mutation (S1710L) in one symptomatic IVF patient that did not exhibit the typical Brugada ECG.