Short QT syndrome

Gene: SLC22A5

Red List (low evidence)

SLC22A5 (solute carrier family 22 member 5)
EnsemblGeneIds (GRCh38): ENSG00000197375
EnsemblGeneIds (GRCh37): ENSG00000197375
OMIM: 603377, Gene2Phenotype
SLC22A5 is in 17 panels

7 reviews

Juan Pablo Kaski (Great Ormond Street Hospital/UCL)

Green List (high evidence)

Some evidence (published and anecdotal) to suggest causative role in SQTS in the context of primary carnitine deficiency (including in the absence of heart muscle disease).
Created: 27 Nov 2019, 12:17 p.m. | Last Modified: 27 Nov 2019, 12:17 p.m.
Panel Version: 1.23

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Ivone Leong (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Demoted from Green to Red as the GMS Cardiology specialist group feels that this gene should not be on this panel.
Created: 27 Nov 2019, 1:10 p.m. | Last Modified: 27 Nov 2019, 1:10 p.m.
Panel Version: 1.24
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, 2:46 p.m. | Last Modified: 18 Nov 2019, 2:46 p.m.
Panel Version: 1.23
Comment on mode of inheritance: Phenotype changed due to expert reviews.
Created: 30 Sep 2019, 12:24 p.m. | Last Modified: 30 Sep 2019, 12:24 p.m.
Panel Version: 1.21

James Eden (Manchester)

Red List (low evidence)

Literature associates with SQTS secondary to carnitine deficiency.
Created: 27 Sep 2019, 1:56 p.m. | Last Modified: 27 Sep 2019, 1:56 p.m.
Panel Version: 1.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Carnitine deficiency, systemic primary 212140

Publications

Rebecca Whittington (South West GLH)

Red List (low evidence)

Carnitine deficiency, systemic primary 212140
Created: 25 Mar 2019, 4:30 p.m.
Not associated with SQT
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Ellen McDonagh (Genomics England Curator)

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.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

I don't know

Mutations in this gene cause carnitine definciency. Clinical characteristics are primarily hepatic and cerebral dysfunction lethargy and hypoglycaemia. Cardiomyopathy is also a feature. No evidence that mutations in this gene cause primary or isolated Short QT syndrome.
Created: 25 Jan 2019, 12:52 p.m.

Jules Hancox (University of Bristol)

Green List (high evidence)

SLC22A5 loss of function mutations lead to defective OCTN2, which leads to primary carnitine deficiency.

PCD has been recognised for a long time. Autosomal recessive, although some heterozygotes can display symptoms. PCD impairs carnitine uptake into cardiac myocytes, leads to impaired long chain fatty acid uptake into mitochondria. It leads to a cardiomyopathy (dilated) and there is an association with arrhytomogenesis. There is now good evidence that PCD produces a short QT phenoype in humans and in an animal model, though the precise mechanism is unknown. It is important to include SLC22A5 screening on a panel for SQTS, particularly where there is evidence for cardiomyopathy, because when it is identified it can be treated with dietary L-carnitine supplementation.

Additional case report: https://www.hindawi.com/journals/cric/2018/3232105/
Sources: Literature
Created: 17 Oct 2018, 9:47 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency

Publications

History Filter Activity

27 Nov 2019, Gel status: 1

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: slc22a5 has been classified as Red List (Low Evidence).

30 Sep 2019, Gel status: 3

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: SLC22A5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

13 Sep 2019, Gel status: 3

Added New Source

Ivone Leong (Genomics England Curator)

Source West Midlands, Oxford and Wessex GLH was added to SLC22A5.

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to SLC22A5. Mode of inheritance for gene SLC22A5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to SLC22A5.

20 Nov 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Jules Hancox: SLC22A5 loss of function mutat

19 Nov 2018, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SLC22A5 were changed from arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency to arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency; Carnitine deficiency, systemic primary 212140

19 Nov 2018, Gel status: 4

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SLC22A5 were set to PMID: 7254270; 7131143; 26190315; 29198778

15 Nov 2018, Gel status: 3

Added New Source, Set mode of inheritance, Status Update

Sarah Leigh (Genomics England Curator)

Source Expert Review Green was added to SLC22A5. Mode of inheritance for gene SLC22A5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Rating Changed from No List (delete) to Green List (high evidence)

17 Oct 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Jules Hancox (University of Bristol)

gene: SLC22A5 was added gene: SLC22A5 was added to Short QT syndrome. Sources: Literature Mode of inheritance for gene: SLC22A5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLC22A5 were set to PMID: 7254270; 7131143; 26190315; 29198778 Phenotypes for gene: SLC22A5 were set to arrhythmia; short QT; cardiomyopathy; primary carnitine deficiency Review for gene: SLC22A5 was set to GREEN