Long QT syndrome

Gene: KCNJ5

Red List (low evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel.

Created: 18 Nov 2019, 2:09 p.m. | Last Modified: 18 Nov 2019, 2:09 p.m.

Panel Version: 1.44

I don't know

Gene currently tested on Manchester cardiac gene panel. 16 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: gene not curated (accessed 29/01/2019).

Created: 19 Sep 2019, 9:53 a.m. | Last Modified: 19 Sep 2019, 9:53 a.m.

Panel Version: 1.38

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Long QT syndrome 13 (613485); Hyperaldosteronism, familial, type III (613677)

Publications

• 23872692

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

Green List (high evidence)

Hyperaldosteronism, familial, type III (OMIM 613677), Long QT syndrome 13 (OMIM 613485).

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

Literature evidence includes a large Chinese Pedigree. PMID:20560207. PMID:25322277. PMID: 24574546.

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

Red List (low evidence)

Gene currently on Royal Brompton diagnostic panel, only a few VUS reported. Low literature evidence based on small number of cases (mainly Wang et al. (2013) Heart Rhythm 10:1500-1506).

Created: 19 Mar 2019, 4:06 p.m. | Last Modified: 19 Sep 2019, 9:15 a.m.

Panel Version: 1.38

Green List (high evidence)

Comment on list classification: On Manchester diagnostic panel

Created: 7 Mar 2016, 4:25 p.m.

I don't know

Comment on list classification: Due to limited evidence for causation of Long QT syndrome, the decision was made to demote this gene from Green to Red in the NHSE GMS Cardiology Specialist Group meeting call on 25th January 2019.

Created: 4 Mar 2019, 9:09 p.m.

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 = 1.

Created: 19 Feb 2016, 11:04 a.m.

Comment when marking as ready: Good evidence from OMIM as well

Created: 1 Feb 2016, 9:02 p.m.

Red List (low evidence)

This gene is linked to LQTS based on a large Chinese family with the p.Gly387Arg variant (Wang et al. (2013) HeartRhythm 10:1500_1506 Yang et al. 2010 American Journal of Human Genetics 86:872-880). However this variant is present in 47 out of 9424 South Asians in GnomAD (0.5 percent). Oxford lab classify as VUS. Therefore no evidence to support that variants in this gene cause LQTS.

Created: 25 Jan 2019, 12:41 p.m.

1 large 4 generational chinese family reported to have a variant in this gene; however, that variant is present in 0.4% of East Asian individuals on ExAC. Other reported variants appear to be associated with hyperaldosteronism.

Created: 3 Mar 2016, 9:13 a.m.

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