Long QT syndrome
Gene: CACNA1C
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
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
Gene on Royal Brompton LQTS panel, some association with isolated LQTS in literature (25633834, 24728418). (Likely)Pathogenic variants detected in our labCreated: 19 Mar 2019, 12:03 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Timothy syndrome (601005)
Publications
Variants in this GENE are reported as part of current diagnostic practice
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
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.
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 pathogenicityCreated: 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-QTCreated: 29 Jan 2016, 1:20 p.m.
Gain of function for Timothy 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
many mutations identified in this gene associated with phenotype (published)
experience of this in our lab tooCreated: 2 Dec 2015, 4:23 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Phenotypes for gene: CACNA1C were changed from Brugada syndrome 3 (611875); Timothy syndrome (601005) to Timothy syndrome, OMIM:601005; Timothy syndrome, MONDO:0010979; Long QT syndrome 8, OMIM:618447; long qt syndrome 8, MONDO:0032756; Brugada syndrome 3, OMIM:611875; Brugada syndrome 3, MONDO:0012742; CACNA1C-related disorder
Publications for gene: CACNA1C were set to 18250309
Source South West GLH was added to CACNA1C.
Source London South GLH was added to CACNA1C.
Source North West GLH was added to CACNA1C. Added phenotypes Brugada syndrome 3 (611875); Timothy syndrome (601005) for gene: CACNA1C Publications for gene CACNA1C were changed from 15454078 to 18250309 Rating Changed from Green List (high evidence) to Green List (high evidence)
Mode of inheritance for CACNA1C was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for CACNA1C were set to 15454078
CACNA1C was added to Long QT syndromepanel. Sources: UKGTN
CACNA1C was added to Long QT syndromepanel. Sources: Expert list,Emory Genetics Laboratory
CACNA1C was added to Long QT syndromepanel. Sources: Expert list,Emory Genetics Laboratory