Long QT syndrome

Gene: SCN5A

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

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

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

• 29798782

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

• 19716085

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

Green List (high evidence)

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

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.

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