Andersen-Tawil syndrome

Andersen-Tawil syndrome (ATS) is characterized by a triad of episodic flaccid muscle weakness (i.e., periodic paralysis), ventricular arrhythmias and prolonged QT interval, and anomalies including low-set ears, widely spaced eyes, small mandible, fifth-digit clinodactyly, syndactyly, short stature, and scoliosis [22]. Two types of Andersen-Tawil syndrome are distinguished by their genetic causes. Type 1, which accounts for about 60 percent of all cases of the disorder, is caused by mutations in the KCNJ2 gene [23]. The remaining 40 percent of cases are designated as type 2; the cause of these cases are as yet unknown  [23].

Gene name  Transcript Clinical sensitivity
KCNJ2 ENST00000535240 ~60% [22]

Brugada syndrome (BrS)

Brugada syndrome (BrS) is an autosomal dominantly inherited arrhythmia syndrome, with highly variable expressivity and penetrance [24]. Cardiac symptoms are characterised by abnormal findings on the electrocardiogram (ECG) in conjunction with an increased risk of ventricular arrhythmias and sudden cardiac death. It has an estimated prevalence of approximately 1:2000 [25]There is limited data regarding the prevalence and population distribution of Brugada syndrome but data suggests significant population variance according to ethnicity, with males often being more severely affected. Brugada syndrome is thought to account for up to 4% of all sudden cardiac deaths in the setting of a structurally normal heart [26]. Loss-of-function mutations in SCN5A are the most frequent genetic alteration identified in Brugada syndrome, with pathogenic variants being identified in about 35% of cases [27]

Gene name  Transcript Clinical sensitivity
SCN5A ENST00000333535 10-30% [26-29]
CACNA1C ENST00000399655 6-7% [27
CACNB2  ENST00000377329  4-5% [27]
CACNA2D1 ENST00000356860 <1% [29
GPD1L ENST00000828541 <1% [27,29
KCND3 ENST00000315987  <1% [29]
SCN1B  ENST00000262631  1-2% [27
PKP2  ENST00000070846  n/a
HCN4  ENST00000261917  <1% [27,29
KCNE3 ENST00000310128 <1% [27,29
RANGRF  ENST00000226105 <1% [29
SCN3B  ENST00000392770 <1% [27,29]

Catecholaminergic  polymorphic ventricular tachycardia (CPVT)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by cardiac electrical instability exacerbated by acute activation of the adrenergic nervous system [30]. If untreated, the disease can be lethal, as approximately 30% of those affected experience at least one cardiac arrest [30]. Patients usually present before the age of 10 [25]. The true prevalence of CPVT in the population is not known but is estimated at approximately 1:10,000 [30]Autosomal dominantly inherited pathogenic variants in RYR2 (most common) and recessively inherited CASQ2 pathogenic variants account for most genetic causes. Causative allelic variants are identified in approximately 55%-65% of individuals with CPVT [28].

Gene name  Transcript Clinical sensitivity
CALM1 ENST00000356978 <1% [30]
CALM2 ENST00000272298  
CALM3 ENST00000291295  
CASQ2 ENST00000261448  2-5% [28,30
RYR2 ENST00000366574  50-60% [28,30,31
TRDN ENST00000398178  n/a 

Long QT syndrome

Long QT Syndrome (LQTS) is an autosomal dominantly inherited disorder of ventricular repolarisation, with an estimated prevalence of 1:2000 [25]. It is characterised by a prolonged QT interval on ECG and predisposition to cardiac arrhythmia, syncope and sudden death. LQTS is a genetically heterogenous condition, but the most common causes are heterozygous pathogenic variants in the KCNQ1, KCNH2, and SCN5A genes. A causal variant is found in approximately 75% of LQTS patients with a definitive diagnosis [32]. Around 15% of these pathogenic variants are de novo, and compound heterozygous pathogenic variants are found in 10% of genotype-positive patients, often presenting with a more severe clinical manifestation [32]. Variable penetrance may be observed within families. The autosomal recessive syndromic form of LQTS, known as Jervell and Lange-Nielsen syndrome, probably affects less than 1 in a million people and is accompanied by sensorineural deafness. It is caused by biallelic pathogenic variants in the KCNQ1 or KCNE1 genes [28].  

Gene name Transcript Clinical sensitivity
KCNQ1 ENST00000155840 30-55% [24,25,28,32,33]
KCNH2 ENST00000262182  25-45% [24,25,28,32,33
SCN5A  ENST00000333535 5-13% [24,25,28,32,33
KCNE1  ENST00000399289 1-1.7% [25,33]
KCNE2 ENST00000290310 0.7-1% [25,33]
ANK2 ENST00000264366 ~1% [25
CACNA1C ENST00000399655 n/a
CALM1  ENST00000356978 n/a
CAV3 ENST00000343849 n/a
KCNJ2 ENST00000353240  n/a
KCNJ5 ENST00000529694 n/a
RYR2 ENST00000366574  n/a
SCN4B ENST00000324727  n/a
SNTA1  ENST00000217381 n/a

Short QT syndrome

Short QT syndrome (SQTS) is marked by a shortened QT interval and an increased risk of atrial and/or ventricular arrhythmias [25], however the severity of clinical manifestations is highly variable. It is autosomal dominantly inherited and genetically heterogeneous [28]. Gain-of-function variants in KCNH2, KCNQ1, and KCNJ2 are the principal genetic causes of SQTS [27]. As SQTS is rare, data on its prevalence and demographics are limited. The identification of a pathogenic variant causing SQTS ranges from 18% to 40% in the literature but the yield of clinical genetic test­ing is likely to be much lower due to a publication bias for more severe cases [27].

Gene name Transcript Clinical sensitivity
KCNH2 ENST00000262182 18-33% [27]
KCNJ2 ENST00000353240  <5% [27
KCNQ1 ENST00000155840  <5% [27
CACNA1C  ENST00000399655  n/a
CACNA2D1 ENST00000356860 n/a
CACNB2  ENST00000377329  n/a
SLC22A5 ENST00000435065  

Other genes included under all arrhythmia

Gene name Transcript Clinical sensitivity
ABCC9 ENST00000261201 n/a
AKAP9 ENST00000356239  n/a
DSC2  ENST00000280904  n/a
EMD ENST00000369842  n/a
GJA5  ENST00000271348 n/a
JPH2 ENST00000372980  n/a
KCNA5  ENST00000252321 n/a
LMNA  ENST00000368300  n/a
MYH6  ENST00000356287  n/a
NKX2-5 ENST00000329198  n/a
NPPA  ENST00000376480 n/a
SCN10A ENST00000449082  


Clinical genetics and genomics laboratory 

Ground floor (level 2), Sydney wing, Royal Brompton Hospital, Sydney Street, London, SW3 6NP

Telephone: +44(0)207 352 8121, ext 83009

Email: or 

Opening hours: Monday to Friday, 9am to 5pm

Head of laboratory: Dr Deborah Morris-Rosendahl

Useful documents

Molecular genetic testing request and consent form (pdf, 431KB)

Non-NHS molecular genetic testing request and consent form (pdf, 493KB)