Description
Eligibility statement for Long QT syndrome (11023):

Relevant diseases:

- Long QT syndrome

Long QT inclusion criteria (29335)
LQTS diagnosed according to criteria*:

- In the presence of an LQTS risk score >= 3.5 in the absence of a secondary cause for QT prolongation

AND/OR

- In the presence of a corrected QT interval for heart rate using Bazett’s formula (QTc) >= 500ms in repeated 12 lead electrocardiogram (ECG) and in the absence of a secondary cause for QT prolongation. 

AND/OR

- In the presence of a QTc between 480 and 499ms in repeated 12-lead ECGs in a patient with unexplained syncope in the absence of a secondary cause for QT prolongation in the absence of a pathogenic mutation.

AND either one of the two criteria below:

- A family history for LQTS with other affected family DNA and phenotype available (at least three over three generations) for linkage studies. 

       OR

- Trio of unaffected parents and severely affected child available (sporadic or recessive)

* Heart Rhythm Society/European Heart Rhythm Association

Individuals with severe or syndromic disease should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease.  In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Long QT exclusion criteria (29335)
- Unclear diagnosis or history suggestive of a non-genetic cause
- Any LQTS mutation positive (if clearly pathogenic)

Prior genetic testing guidance (29335)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Long QT syndrome prior genetic testing genes (29335)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - KCNQ1, KCNH2 and SCN5A

Closing statement (29335)
These requirements will be kept under continual review during the main programme and may be subject to change.

5 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Bill Newman (Manchester Centre for Genomic Medicine)

    Group: other
    Workplace: other

  • Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS diagnostic lab

  • Caroline Wright (Genomics England Curator)

    Group: Other
    Workplace: Genomics England

  • Damian Smedley (Genomics England Curator)

    Group: Other
    Workplace: Other

20 genes

20 reviewed, 10 green

List Gene Reviews Mode of inheritance Details
20 genes
Green Green List (high evidence)
ANK2
5 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert list
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
Phenotypes
  • Long QT syndrome-4
Green Green List (high evidence)
CACNA1C
4 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
  • Expert list
Green Green List (high evidence)
KCNE1
4 reviews
2 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Expert list
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Long QT syndrome-5
Green Green List (high evidence)
KCNE2
5 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Expert list
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Long QT syndrome-6
Green Green List (high evidence)
KCNH2
4 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Long QT syndrome-2
Green Green List (high evidence)
KCNJ2
4 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
  • Expert list
Phenotypes
  • ANDERSEN SYNDROME (170390)
  • LONG QT SYNDROME 7 (170390)
Green Green List (high evidence)
KCNJ5
5 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
  • UKGTN
  • Expert list
Phenotypes
  • Long QT syndrome 13
Green Green List (high evidence)
KCNQ1
4 reviews
2 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Expert list
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Long QT syndrome-1
Green Green List (high evidence)
SCN5A
4 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Expert list
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Long QT syndrome-3
Green Green List (high evidence)
SNTA1
5 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • UKGTN
  • Expert list
Red Red List (low evidence)
AKAP9
4 reviews
2 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • UKGTN
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert list
Phenotypes
  • Long QT syndrome-11
Red Red List (low evidence)
ALG10
3 reviews
1 red
Not set
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • {Acquired long QT syndrome, reduced susceptibility to}, 613688
Red Red List (low evidence)
CALM1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
Phenotypes
  • Long QT syndrome 14
  • Ventricular tachycardia, catecholaminergic polymorphic, 4
Red Red List (low evidence)
CALM2
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
Phenotypes
  • Long QT syndrome 15
Red Red List (low evidence)
CALM3
2 reviews
1 red
Not set
Sources
  • Expert Review Red
Red Red List (low evidence)
CAV3
5 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Red
  • Emory Genetics Laboratory
  • Expert list
Phenotypes
  • Long QT syndrome-9
Red Red List (low evidence)
KCNE3
1 review
Unknown
Sources
  • Literature
Phenotypes
  • Long QT syndrome
  • Brugada syndrome
Red Red List (low evidence)
NOS1AP
3 reviews
1 red
Not set
Sources
  • Expert list
Red Red List (low evidence)
RYR2
1 review
Unknown
Sources
  • Literature
Phenotypes
  • Long QT syndrome
  • Catecholaminergic polymorphic ventricular tachycardia
  • Arrhythmogenic right ventricular cardiomyopathy
Red Red List (low evidence)
SCN4B
3 reviews
2 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • UKGTN
  • Expert list
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Long QT syndrome-10

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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