Long QT syndrome

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 12 panels

8 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Penetrance for this gene has been changed from "complete" to "incomplete" based on PMID: 29728395 and also review from Claire Kirk (UCD).
Created: 12 Jun 2020, 2:12 p.m. | Last Modified: 12 Jun 2020, 2:17 p.m.
Panel Version: 2.15
Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.
Created: 18 Nov 2019, 2:09 p.m. | Last Modified: 18 Nov 2019, 2:09 p.m.
Panel Version: 1.44
Comment on mode of inheritance: MOI was corrected.
Created: 30 Sep 2019, 1:03 p.m. | Last Modified: 30 Sep 2019, 1:03 p.m.
Panel Version: 1.42

Rebecca Whittington (South West GLH)

Green List (high evidence)

Atrial fibrillation, familial, 10 (OMIM 614022), Brugada syndrome 1 (OMIM 601144), Cardiomyopathy, dilated, 1E (OMIM 601154), Heart block, nonprogressive (OMIM 113900), Heart block, progressive, type IA (OMIM 113900), Long QT syndrome-3 (OMIM 603830), Sick sinus syndrome 1 (OMIM 608567), Ventricular fibrillation, familial, 1 (OMIM 603829-AR), {Sudden infant death syndrome, susceptibility to} (OMIM 272120-AR).
Created: 25 Mar 2019, 4:30 p.m.
Established LQT gene - numerous literature evidence. PMID:23098067. PMID: 19716085. PMID: 15840176. https://www.sciencedirect.com/science/article/pii/S097262921730178X.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

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

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

Green List (high evidence)

Gene on Royal Brompton diagnostic panel. LQTS caused by gain of function variants.
Created: 19 Mar 2019, 3:28 p.m.

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

Phenotypes
Atrial fibrillation, familial, 10 614022; Brugada syndrome 1 601144; Cardiomyopathy, dilated, 1E 601154; Heart block, nonprogressive 113900; Heart block, progressive, type IA 113900; Long QT syndrome-3 603830; Sick sinus syndrome 1 608567; Ventricular fibrillation, familial, 1 603829; Sudden infant death syndrome, susceptibility to272120

Publications

James Eden (Manchester)

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. 914 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: association with long QT syndrome 3, definitive association with Brugada syndrome (accessed 29/01/2019).
Created: 14 Feb 2019, 1:38 p.m.

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

Phenotypes
Atrial fibrillation, familial, 10 (614022); Brugada syndrome 1 (601144); Cardiomyopathy, dilated, 1E (601154); Heart block, nonprogressive (113900); Heart block, progressive, type IA (113900); Long QT syndrome-3 (603830); Sick sinus syndrome 1 (608567); Ventricular fibrillation, familial, 1 (603829); {Sudden infant death syndrome, susceptibility to} (272120)

Publications

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

Bill Newman (Manchester Centre for Genomic Medicine)

Green List (high evidence)

Ellen McDonagh (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.
Comment on publications: Promoter variant reported in PMID: 28391114 in a 16-year-old female who died during sleep.
Created: 14 Aug 2017, 1:48 p.m.
On the Inherited Cardiac Condition Genes panel reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.​1007/​s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 266.
Created: 19 Feb 2016, 10:38 a.m.

Publications

  • 7889574
  • doi:10.​1007/​s12265-016-9673-5

Damian Smedley (Genomics England Curator)

Comment when marking as ready: Sufficient expert evidence from OMIM and 2 experts. Not sure on mode of pathogenicty
Created: 29 Jan 2016, 1:18 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Green List (high evidence)

Gain of function for Long QT syndrome
Created: 6 Jan 2016, 5:29 p.m.

Mode of pathogenicity
Other - please provide details in the comments

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Expert list
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Ventricular fibrillation, familial, 1 (603829)
  • Brugada syndrome 1 (601144)
  • Heart block, nonprogressive (113900)
  • Heart block, progressive, type IA (113900)
  • {Sudden infant death syndrome, susceptibility to} (272120)
  • Sick sinus syndrome 1 (608567)
  • Long QT syndrome-3
  • Long QT syndrome-3 (603830)
  • Cardiomyopathy, dilated, 1E (601154)
  • Atrial fibrillation, familial, 10 (614022)
OMIM
600163
Clinvar variants
Variants in SCN5A
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

12 Jun 2020, Gel status: 3

Removed Source, Removed Source, Removed Source, Set Phenotypes, Set penetrance

Ivone Leong (Genomics England Curator)

Source South West GLH was removed from SCN5A. Source London South GLH was removed from SCN5A. Source North West GLH was removed from SCN5A. Phenotypes for gene: SCN5A were changed from Ventricular fibrillation, familial, 1 (603829); Brugada syndrome 1 (601144); Heart block, nonprogressive (113900); Heart block, progressive, type IA (113900); {Sudden infant death syndrome, susceptibility to} (272120); Sick sinus syndrome 1 (608567); Long QT syndrome-3 ; Long QT syndrome-3 (603830); Cardiomyopathy, dilated, 1E (601154); Atrial fibrillation, familial, 10 (614022) to Ventricular fibrillation, familial, 1 (603829); Brugada syndrome 1 (601144); Heart block, nonprogressive (113900); Heart block, progressive, type IA (113900); {Sudden infant death syndrome, susceptibility to} (272120); Sick sinus syndrome 1 (608567); Long QT syndrome-3; Long QT syndrome-3 (603830); Cardiomyopathy, dilated, 1E (601154); Atrial fibrillation, familial, 10 (614022) Penetrance for gene SCN5A was set from to Complete

12 Jun 2020, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: SCN5A were set to 19716085; 29798782; 26888179; 7889574

30 Sep 2019, Gel status: 3

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: SCN5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

12 Sep 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: SCN5A were set to 19716085

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to SCN5A. Mode of inheritance for gene SCN5A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to SCN5A.

14 Feb 2019, Gel status: 3

Added New Source, Set Phenotypes, Set publications, Status Update

Ellen McDonagh (Genomics England Curator)

Source North West GLH was added to SCN5A. Added phenotypes Ventricular fibrillation, familial, 1 (603829); Brugada syndrome 1 (601144); Heart block, nonprogressive (113900); Heart block, progressive, type IA (113900); {Sudden infant death syndrome, susceptibility to} (272120); Sick sinus syndrome 1 (608567); Long QT syndrome-3 (603830); Cardiomyopathy, dilated, 1E (601154); Atrial fibrillation, familial, 10 (614022) for gene: SCN5A Publications for gene SCN5A were changed from 7889574; doi:10.​1007/​s12265-016-9673-5; 28391114 to 19716085 Rating Changed from Green List (high evidence) to Green List (high evidence)

14 Aug 2017, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for SCN5A were set to 7889574; doi:10.​1007/​s12265-016-9673-5;28391114

29 Jan 2016, Gel status: 4

Gene classified by Genomics England curator

Damian Smedley (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

12 Aug 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN5A was added to Long QT syndromepanel. Sources: Eligibility statement prior genetic testing

13 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SCN5A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SCN5A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SCN5A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene SCN5A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list

13 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list