Incidentalome

Gene: SCN5A

Green List (high evidence)

SCN5A (sodium voltage-gated channel alpha subunit 5)
EnsemblGeneIds (GRCh38): ENSG00000183873
EnsemblGeneIds (GRCh37): ENSG00000183873
OMIM: 600163, Gene2Phenotype
SCN5A is in 16 panels

3 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Variants in this gene are also associated with a range of arrhythmia disorders.
Created: 12 Aug 2022, 1:46 a.m. | Last Modified: 12 Aug 2022, 1:46 a.m.
Panel Version: 0.155
DEFINITIVE by ClinGen:
SCN5A was first reported in relation to autosomal dominant dilated cardiomyopathy (DCM) in 2005 (Olson et al., 2005, PMID: 15671429). Human genetic evidence supporting this gene-disease relationship includes case-level data and segregation data. Numerous variants (missense, frameshift, nonsense) have been reported in humans with isolated DCM (Olson et al., 2005, PMID: 15671429; Ge et al., 2008, PMID: 19808398; McNair et al., 2011, PMID: 21596231; Morales et al., 2011, PMID: 20458009; Grosselin-Badaroudine et al., 2012, PMID: 22675453; Laurent et al., 2012, PMID: 22766342; Mann et al., 2012, PMID: 22999724; Zakrzewska-Koperska et al., 2018, PMID: 29871609; Calloe et al., 2018, PMID: 29506689; Gigli et al., 2019, PMID: 31514951; Doisne et al., 2020, PMID: 31930659). This gene-disease association is supported by mouse models, a human iPS cell culture model, and expression studies. SCN5A mRNA levels were markedly decreased in heart tissues obtained from DCM patients (Kepenek et al., 2019, PMID: 31520233). The myosin heavy chain-Snail transgenic mice displayed a DCM phenotype with conduction block and marked reduction of SCN5A expression (Hesse, et al., 2007, PMID: 17512504). Heterozygous and homozygous knock-in mouse models harboring SCN5A p.D1275N displayed a DCM phenotype including intraventricular conduction block with marked reduction of cardiac sodium currents (Watanabe et al., 2011, PMID: 21824921). Furthermore, patient-derived human iPS cell-induced cardiomyocytes carrying SCN5A p.R219H showed reduced contraction, prolonged action potential duration, early afterdepolarization, and H+-leak currents (Moreau et al., 2018, PMID: 30218094).
Created: 26 Mar 2021, 9:14 a.m. | Last Modified: 26 Mar 2021, 9:14 a.m.
Panel Version: 0.101

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Long QT syndrome 3 (MIM#603830); Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome 1, MIM# 601144; Heart block, progressive, type IA, MIM# 113900

Publications

Ivan Macciocca (Victorian Clinical Genetics Services)

Green List (high evidence)

definitive as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group
Created: 31 May 2020, 2:13 p.m. | Last Modified: 31 May 2020, 2:13 p.m.
Panel Version: 0.7

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
long QT syndrome; Brugada syndrome; dilated cardiomyopathy

Publications

Variants in this GENE are reported as part of current diagnostic practice

Crystle Lee (Victorian Clinical Genetics Services)

Green List (high evidence)

Well-reported gene/disease association.

Long QT associated with gain-of-function variants (PMID: 29798782)
Created: 28 Feb 2020, 4:52 a.m. | Last Modified: 28 Feb 2020, 4:52 a.m.
Panel Version: 0.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Long QT syndrome 3 (MIM#603830)

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
  • Victorian Clinical Genetics Services
Phenotypes
  • Long QT syndrome 3 (MIM#603830)
  • Sick sinus syndrome 1, MIM# 608567
  • Ventricular fibrillation, familial, 1, MIM# 603829
  • Brugada syndrome 1, MIM# 601144
  • Heart block, progressive, type IA, MIM# 113900
  • Cardiomyopathy, dilated, 1E, MIM# 601154
Tags
cardiac
OMIM
600163
Clinvar variants
Variants in SCN5A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Aug 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: scn5a has been classified as Green List (High Evidence).

12 Aug 2022, Gel status: 3

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag cardiac tag was added to gene: SCN5A.

12 Aug 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: SCN5A were changed from to Long QT syndrome 3 (MIM#603830); Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome 1, MIM# 601144; Heart block, progressive, type IA, MIM# 113900; Cardiomyopathy, dilated, 1E, MIM# 601154

12 Aug 2022, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: SCN5A were set to

12 Aug 2022, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: SCN5A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: SCN5A was added gene: SCN5A was added to Incidentalome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: SCN5A was set to Unknown