Long QT syndrome
Gene: SCN5A
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
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
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
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
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
Comment when marking as ready: Sufficient expert evidence from OMIM and 2 experts. Not sure on mode of pathogenictyCreated: 29 Jan 2016, 1:18 p.m.
Gain of function for Long QT syndromeCreated: 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
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
Publications for gene: SCN5A were set to 19716085; 29798782; 26888179; 7889574
Mode of inheritance for gene: SCN5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCN5A were set to 19716085
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
Source London South GLH was added to SCN5A.
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)
Publications for SCN5A were set to 7889574; doi:10.1007/s12265-016-9673-5;28391114
This gene has been classified as Green List (High Evidence).
SCN5A was added to Long QT syndromepanel. Sources: Eligibility statement prior genetic testing
Model of inheritance for gene SCN5A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list
Model of inheritance for gene SCN5A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list
Model of inheritance for gene SCN5A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list
Model of inheritance for gene SCN5A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list
SCN5A was added to Long QT syndromepanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Expert list