VCV000067639.24 - ClinVar

NM_000335.5(SCN5A):c.1127G>A (p.Arg376His)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(8)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000335.5(SCN5A):c.1127G>A (p.Arg376His)

Variation ID: 67639 Accession: VCV000067639.24

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p22.2 3: 38606682 (GRCh38) [ NCBI UCSC ] 3: 38648173 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 9, 2014	Sep 16, 2024	Apr 24, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000335.5:c.1127G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000326.2:p.Arg376His	missense
NM_001099404.2:c.1127G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001092874.1:p.Arg376His	missense
NM_001099405.2:c.1127G>A	NP_001092875.1:p.Arg376His	missense
NM_001160160.2:c.1127G>A	NP_001153632.1:p.Arg376His	missense
NM_001160161.2:c.1127G>A	NP_001153633.1:p.Arg376His	missense
NM_001354701.2:c.1127G>A	NP_001341630.1:p.Arg376His	missense
NM_198056.3:c.1127G>A	NP_932173.1:p.Arg376His	missense
NC_000003.12:g.38606682C>T
NC_000003.11:g.38648173C>T
NG_008934.1:g.47991G>A
LRG_289:g.47991G>A
LRG_289t1:c.1127G>A	LRG_289p1:p.Arg376His
	Q14524:p.Arg376His

... more HGVS ... less HGVS

Protein change

R376H

Other names

p.R376H:CGC>CAC

Canonical SPDI

NC_000003.12:38606681:C:T

Functional
consequence

The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele
frequency (GMAF)

The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency

The frequency of the allele represented by this VCV record.

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Exome Aggregation Consortium (ExAC) 0.00000

The Genome Aggregation Database (gnomAD), exomes 0.00001

The Genome Aggregation Database (gnomAD) 0.00003

Trans-Omics for Precision Medicine (TOPMed) 0.00003

Links

ClinGen: CA014389

UniProtKB: Q14524#VAR_055169

dbSNP: rs199473101

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SCN5A		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3773	4212

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Brugada syndrome	not provided (1)	criteria provided, single submitter	-	RCV000058396.15
not provided	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Apr 24, 2024	RCV000182960.18
Cardiovascular phenotype	Likely pathogenic (1)	criteria provided, single submitter	Jan 10, 2024	RCV000617435.11
Cardiac arrhythmia	Pathogenic (1)	criteria provided, single submitter	Aug 8, 2023	RCV001842271.11
Atrial fibrillation, familial, 10 Brugada syndrome 1 Dilated cardiomyopathy 1E Long QT syndrome 3 Progressive familial heart block, type 1A SUDDEN INFANT DEATH SYNDROME Sick sinus syndrome 1 Ventricular fibrillation, paroxysmal familial, type 1	Pathogenic (1)	criteria provided, single submitter	Nov 12, 2021	RCV002498339.8
Atrial fibrillation, familial, 10 Brugada syndrome 1 Dilated cardiomyopathy 1E Long QT syndrome 3 Progressive familial heart block, type 1A Sick sinus syndrome 1 Ventricular fibrillation, paroxysmal familial, type 1	Likely pathogenic (1)	criteria provided, single submitter	Nov 11, 2021	RCV003457639.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Apr 24, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000235357.17 First in ClinVar: Jul 05, 2015 Last updated: Sep 16, 2024	Comment: Published functional studies demonstrate this variant results in a significant reduction of the inward sodium current (PMID: 15851228, 21840964, 24295898); Not observed at significant frequency … (more) Published functional studies demonstrate this variant results in a significant reduction of the inward sodium current (PMID: 15851228, 21840964, 24295898); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17512504, 20129283, 28341781, 34461752, 15851228, 23414114, 25194972, 18378609, 16344400, 23671135, 27930701, 21840964, 31737537, 30193851, 30662450, 29709101, 33164571, 33131149, 30203441, 34495297, 24295898) (less)
Pathogenic (Nov 12, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Progressive familial heart block, type 1A SUDDEN INFANT DEATH SYNDROME Brugada syndrome 1 Dilated cardiomyopathy 1E Ventricular fibrillation, paroxysmal familial, type 1 Long QT syndrome 3 Sick sinus syndrome 1 Atrial fibrillation, familial, 10 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002814864.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Likely pathogenic (Nov 11, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Atrial fibrillation, familial, 10 Brugada syndrome 1 Dilated cardiomyopathy 1E Progressive familial heart block, type 1A Long QT syndrome 3 Sick sinus syndrome 1 Ventricular fibrillation, paroxysmal familial, type 1 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. (Autosomal dominant inheritance) Affected status: no Allele origin: germline	Division Of Personalized Genomic Medicine, Columbia University Irving Medical Center Accession: SCV004190147.1 First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023	Publications: PubMed (9) PubMed: 24295898‚ 15851228‚ 16344400‚ 28341781‚ 20129283‚ 18378609‚ 27930701‚ 25194972‚ 23671135 Comment: The c.1127G>A variant in theSCN5A gene is a heterozygous missense variant, which results in the substitution of the highly conserved arginine residue at the 376 … (more) The c.1127G>A variant in theSCN5A gene is a heterozygous missense variant, which results in the substitution of the highly conserved arginine residue at the 376 position to histidine p.(Arg376His). The following criteria was used in classifying this variant: This variant localizes to coding exon 9 of the SCN5A gene (27 exons in total;NM_001160161.2). Functional studies of the variant showed reduction of the inward sodium current in cells expressing the p.Arg376His variant compared with the wildtype, which is consistent with a Brugada syndrome pattern (PMID: 24295898). This variant has been observed in the Genome Aggregation Database (gnomAD) at a very low frequency (2/247,596, 0 homozygotes), indicating it is not a common benign variant in the populations represented in this database. This variant has been reported in the literature segregating with disease in one family affected with Brugada syndrome/conduction disease (PMID: 15851228), in several individuals affected with Brugada syndrome (PMID: 16344400, 28341781), in individuals referred for Brugada genetic testing (PMID: 20129283), atrial fibrillation (PMID: 18378609), hypertrophic cardiomyopathy (PMID: 27930701), in individuals referred for Brugada genetic testing (PMID: 20129283), and in individuals who suffered sudden unexplained death (PMID: 25194972, 23671135). (less) Clinical Features: Hemolytic-uremic syndrome (present) , Inflammation of the large intestine (present) , Renal insufficiency (present) Age: 40-49 years Sex: female
Pathogenic (Feb 26, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002020029.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Dec 17, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000760186.6 First in ClinVar: Jun 09, 2014 Last updated: Feb 14, 2024	Publications: PubMed (11) PubMed: 28492532‚ 15851228‚ 16344400‚ 18378609‚ 20129283‚ 23671135‚ 25194972‚ 27930701‚ 28341781‚ 21840964‚ 24295898 Comment: This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 376 of the SCN5A protein (p.Arg376His). … (more) This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 376 of the SCN5A protein (p.Arg376His). This variant is present in population databases (rs199473101, gnomAD 0.004%). This missense change has been observed in individuals with Brugada syndrome (PMID: 15851228, 16344400, 18378609, 20129283, 23671135, 25194972, 27930701, 28341781). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 67639). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SCN5A function (PMID: 15851228, 21840964, 24295898). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Aug 08, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiac arrhythmia Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV001359848.3 First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024	Publications: PubMed (13) PubMed: 15851228‚ 16344400‚ 18378609‚ 20129283‚ 21840964‚ 23671135‚ 24295898‚ 25194972‚ 26713557‚ 27930701‚ 28341781‚ 29709101‚ 32893267 Comment: This missense variant replaces arginine with histidine at codon 376 of the SCN5A protein. This variant is found within the highly conserved pore-forming region of … (more) This missense variant replaces arginine with histidine at codon 376 of the SCN5A protein. This variant is found within the highly conserved pore-forming region of transmembrane domain DI (a.a. 277-389). Rare nontruncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome (PMID: 32893267). Functional studies have shown that this variant significantly reduces sodium channel currents (PMID: 15851228, 21840964, 24295898, 26713557). This variant has shown a highly variable phenotypic presentation ranging from Brugada syndrome to conduction disease in 9 members from a single family (PMID: 15851228). This variant has been reported in multiple other individuals affected with Brugada syndrome or referred for Brugada syndrome genetic testing (PMID: 16344400, 20129283, 28341781, 29709101) in an individual affected with atrial fibrillation (PMID: 18378609) and in individuals affected with sudden death (PMID: 23671135, 25194972, 27930701). This variant has been identified in 2/247596 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
Likely pathogenic (Jan 10, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000737601.5 First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024	Publications: PubMed (14) PubMed: 15851228‚ 16344400‚ 18378609‚ 20129283‚ 21109022‚ 23671135‚ 24295898‚ 25194972‚ 26713557‚ 27930701‚ 28341781‚ 29709101‚ 33164571‚ 34461752 Comment: The p.R376H variant (also known as c.1127G>A), located in coding exon 8 of the SCN5A gene, results from a G to A substitution at nucleotide … (more) The p.R376H variant (also known as c.1127G>A), located in coding exon 8 of the SCN5A gene, results from a G to A substitution at nucleotide position 1127. The arginine at codon 376 is replaced by histidine, an amino acid with highly similar properties. This variant has been detected in multiple individuals with Brugada syndrome (BrS; Rossenbacker T et al. Heart Rhythm. 2004;1(5):610-5; Frustaci A et al. Circulation. 2005;112(24):3680-7; Kapplinger JD et al. Heart Rhythm. 2010;7(1):33-46). It has also been identified in an individual with atrial fibrillation (Darbar D et al. Circulation. 2008;117(15):1927-35) and in families with a history of sudden death (Papadakis M et al. Circ Arrhythm Electrophysiol. 2013;6(3):588-96; Wong LC et al. Circ Arrhythm Electrophysiol. 2014;7(5):800-6). Additionally, p.R376H has been shown to disrupt protein function, resulting in reduced sodium channel current (Rossenbacker T et al. Heart Rhythm 2004;1(5):610-5; Shinlapawittayatorn K et al. Heart Rhythm 2011; 8(3):455-62; Detta N et al. Int. J. Cardiol. 2014; 170(3):e63-5; Peters CH et al. Mol. Biol. 2016;120(1-3):77-88). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
not provided (-)	no classification provided Method: literature only	Brugada syndrome Affected status: unknown Allele origin: germline	Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust Accession: SCV000089916.3 First in ClinVar: Oct 22, 2013 Last updated: Jun 09, 2014	Publications: PubMed (5) PubMed: 22581653‚ 15851228‚ 16344400‚ 20129283‚ 18378609 Comment: This variant has been reported as associated with Brugada syndrome in the following publications (PMID:15851228;PMID:16344400;PMID:20129283;PMID:18378609). This is a literature report, and does not necessarily reflect … (more) This variant has been reported as associated with Brugada syndrome in the following publications (PMID:15851228;PMID:16344400;PMID:20129283;PMID:18378609). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. (less)

Comment:

Published functional studies demonstrate this variant results in a significant reduction of the inward sodium current (PMID: 15851228, 21840964, 24295898); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17512504, 20129283, 28341781, 34461752, 15851228, 23414114, 25194972, 18378609, 16344400, 23671135, 27930701, 21840964, 31737537, 30193851, 30662450, 29709101, 33164571, 33131149, 30203441, 34495297, 24295898)

Comment:

The c.1127G>A variant in theSCN5A gene is a heterozygous missense variant, which results in the substitution of the highly conserved arginine residue at the 376 position to histidine p.(Arg376His). The following criteria was used in classifying this variant: This variant localizes to coding exon 9 of the SCN5A gene (27 exons in total;NM_001160161.2). Functional studies of the variant showed reduction of the inward sodium current in cells expressing the p.Arg376His variant compared with the wildtype, which is consistent with a Brugada syndrome pattern (PMID: 24295898). This variant has been observed in the Genome Aggregation Database (gnomAD) at a very low frequency (2/247,596, 0 homozygotes), indicating it is not a common benign variant in the populations represented in this database. This variant has been reported in the literature segregating with disease in one family affected with Brugada syndrome/conduction disease (PMID: 15851228), in several individuals affected with Brugada syndrome (PMID: 16344400, 28341781), in individuals referred for Brugada genetic testing (PMID: 20129283), atrial fibrillation (PMID: 18378609), hypertrophic cardiomyopathy (PMID: 27930701), in individuals referred for Brugada genetic testing (PMID: 20129283), and in individuals who suffered sudden unexplained death (PMID: 25194972, 23671135).

Comment:

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 376 of the SCN5A protein (p.Arg376His). This variant is present in population databases (rs199473101, gnomAD 0.004%). This missense change has been observed in individuals with Brugada syndrome (PMID: 15851228, 16344400, 18378609, 20129283, 23671135, 25194972, 27930701, 28341781). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 67639). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SCN5A function (PMID: 15851228, 21840964, 24295898). For these reasons, this variant has been classified as Pathogenic.

Comment:

This missense variant replaces arginine with histidine at codon 376 of the SCN5A protein. This variant is found within the highly conserved pore-forming region of transmembrane domain DI (a.a. 277-389). Rare nontruncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome (PMID: 32893267). Functional studies have shown that this variant significantly reduces sodium channel currents (PMID: 15851228, 21840964, 24295898, 26713557). This variant has shown a highly variable phenotypic presentation ranging from Brugada syndrome to conduction disease in 9 members from a single family (PMID: 15851228). This variant has been reported in multiple other individuals affected with Brugada syndrome or referred for Brugada syndrome genetic testing (PMID: 16344400, 20129283, 28341781, 29709101) in an individual affected with atrial fibrillation (PMID: 18378609) and in individuals affected with sudden death (PMID: 23671135, 25194972, 27930701). This variant has been identified in 2/247596 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

Comment:

The p.R376H variant (also known as c.1127G>A), located in coding exon 8 of the SCN5A gene, results from a G to A substitution at nucleotide position 1127. The arginine at codon 376 is replaced by histidine, an amino acid with highly similar properties. This variant has been detected in multiple individuals with Brugada syndrome (BrS; Rossenbacker T et al. Heart Rhythm. 2004;1(5):610-5; Frustaci A et al. Circulation. 2005;112(24):3680-7; Kapplinger JD et al. Heart Rhythm. 2010;7(1):33-46). It has also been identified in an individual with atrial fibrillation (Darbar D et al. Circulation. 2008;117(15):1927-35) and in families with a history of sudden death (Papadakis M et al. Circ Arrhythm Electrophysiol. 2013;6(3):588-96; Wong LC et al. Circ Arrhythm Electrophysiol. 2014;7(5):800-6). Additionally, p.R376H has been shown to disrupt protein function, resulting in reduced sodium channel current (Rossenbacker T et al. Heart Rhythm 2004;1(5):610-5; Shinlapawittayatorn K et al. Heart Rhythm 2011; 8(3):455-62; Detta N et al. Int. J. Cardiol. 2014; 170(3):e63-5; Peters CH et al. Mol. Biol. 2016;120(1-3):77-88). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

Comment:

This variant has been reported as associated with Brugada syndrome in the following publications (PMID:15851228;PMID:16344400;PMID:20129283;PMID:18378609). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Genotype-Phenotype Correlation of SCN5A Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands.	Milman A	Circulation. Genomic and precision medicine	2021	PMID: 34461752
Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.	Walsh R	Genetics in medicine : official journal of the American College of Medical Genetics	2021	PMID: 32893267
SCN5A Mutation Type and a Genetic Risk Score Associate Variably With Brugada Syndrome Phenotype in SCN5A Families.	Wijeyeratne YD	Circulation. Genomic and precision medicine	2020	PMID: 33164571
Genotype-phenotype relationship and risk stratification in loss-of-function SCN5A mutation carriers.	Robyns T	Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc	2018	PMID: 29709101
Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.	Yamagata K	Circulation	2017	PMID: 28341781
Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.	Sanchez O	PloS one	2016	PMID: 27930701
Triggers for arrhythmogenesis in the Brugada and long QT 3 syndromes.	Peters CH	Progress in biophysics and molecular biology	2016	PMID: 26713557
Cardiac evaluation of pediatric relatives in sudden arrhythmic death syndrome: a 2-center experience.	Wong LC	Circulation. Arrhythmia and electrophysiology	2014	PMID: 25194972
Genetic analysis in a family affected by sick sinus syndrome may reduce the sudden death risk in a young aspiring competitive athlete.	Detta N	International journal of cardiology	2014	PMID: 24295898
Sudden cardiac death with autopsy findings of uncertain significance: potential for erroneous interpretation.	Papadakis M	Circulation. Arrhythmia and electrophysiology	2013	PMID: 23671135
A novel strategy using cardiac sodium channel polymorphic fragments to rescue trafficking-deficient SCN5A mutations.	Shinlapawittayatorn K	Circulation. Cardiovascular genetics	2011	PMID: 21840964
A common SCN5A polymorphism modulates the biophysical defects of SCN5A mutations.	Shinlapawittayatorn K	Heart rhythm	2011	PMID: 21109022
An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing.	Kapplinger JD	Heart rhythm	2010	PMID: 20129283
Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation.	Darbar D	Circulation	2008	PMID: 18378609
Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome.	Frustaci A	Circulation	2005	PMID: 16344400
Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death.	Rossenbacker T	Heart rhythm	2004	PMID: 15851228
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Text-mined citations for rs199473101 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000335.5(SCN5A):c.1127G>A (p.Arg376His)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs199473101 ...