Long QT syndrome

Gene: CACNA1C

Green List (high evidence)

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

Green List (high evidence)

Brugada syndrome 3 (OMIM 611875), Timothy syndrome (OMIM 601005)

Created: 25 Mar 2019, 4:30 p.m.

Literature and functional evidence for this gene. PMID: 25633834. PMID:30023270. PMID:27390944. PMID 24728418.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Green List (high evidence)

Gene on Royal Brompton LQTS panel, some association with isolated LQTS in literature (25633834, 24728418). (Likely)Pathogenic variants detected in our lab

Created: 19 Mar 2019, 12:03 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Timothy syndrome (601005)

Publications

• 18250309
• 25633834
• 24728418

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

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. 74 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: currently no stated association with LQT, disputed association with Brugada syndrome 1 (accessed 29/01/2019).

Created: 14 Feb 2019, 1:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Brugada syndrome 3 (611875); Timothy syndrome (601005)

Publications

• 18250309

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

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.

On the Inherited Cardiac Condition Genes panel for Long QT syndrome 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 = 9.

Created: 19 Feb 2016, 11:03 a.m.

Comment when marking as ready: Not sure on mode of pathogenicity

Created: 29 Jan 2016, 1:24 p.m.

Comment on list classification: 2 expert reviewers, OMIM and G2P confirm this gene caused Timothy syndrome associated with long-QT

Created: 29 Jan 2016, 1:20 p.m.

Green List (high evidence)

Gain of function for Timothy 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

Green List (high evidence)

many mutations identified in this gene associated with phenotype (published)
experience of this in our lab too

Created: 2 Dec 2015, 4:23 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 15454078