Invitae Arrhythmia Comprehensive Panel


Test description

This test provides a comprehensive analysis of the genes associated with inherited arrhythmia conditions. The Invitae Arrhythmia Comprehensive Panel covers primary arrhythmia syndromes, including:

  • long QT syndrome (LQTS)
  • short QT syndrome (SQTS)
  • Brugada syndrome
  • catecholaminergic polymorphic ventricular tachycardia (CPVT)

This panel also includes arrhythmogenic cardiomyopathy conditions, which may present with arrhythmia prior to the development of cardiomyopathy, including:

  • arrhythmogenic right ventricular cardiomyopathy (ARVC)
  • a subset of the genes associated with dilated cardiomyopathy (DCM)
  • a subset of the genes associated with hypertrophic cardiomyopathy (HCM)

Given the clinical overlap between different arrhythmia conditions, comprehensive testing allows for a more efficient evaluation of multiple conditions based on a single indication for testing.

Individuals with clinical symptoms of an inherited arrhythmia may benefit from diagnostic genetic testing to establish or confirm diagnosis, clarify risks, or inform management. Asymptomatic individuals within a family with a known pathogenic variant may also benefit by avoiding activities and medications that can trigger symptoms.

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Primary panel (39 genes)


TTN: Deletion/duplication and sequencing analysis is not offered for exons 153-155 (NM_133378.4).

Add-on preliminary-evidence genes (23 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


ANKRD1: Deletion/duplication analysis is not offered for exons 3 or 4.

Add-on sudden unexpected death in epilepsy (SUDEP) genes (10 genes)

The symptoms associated with arrhythmia and seizures can appear very similar and are known to co-occur in some cases. Some clinicians may wish to include a selection of genes associated with epilepsy for individuals with a differential diagnosis of arrhythmia vs. seizures, or a primary indication of arrhythmia and a family history of seizures.


KCNT1: Deletion/duplication analysis is not offered for exons 26 or 27.

Alternative tests to consider

The Invitae Arrhythmia and Cardiomyopathy Comprehensive Panel has been designed to provide a broad genetic analysis of arrhythmia and cardiomyopathy. Depending on the individual’s clinical and family history, this broader panel may be appropriate. This broader panel can be ordered at no additional cost.

  • arrhythmogenic cardiomyopathy (ARVC)
  • atrial fibrillation
  • Brugada syndrome
  • catecholaminergic polymorphic ventricular tachycardia (CPVT)
  • long QT syndrome (LQTS)
  • short QT syndrome (SQTS)

Arrhythmia is an irregular heart rhythm that occurs when there is a disturbance to the normal electrical impulses in the heart. These electrical disturbances can cause the heart to beat too fast, too slow, or erratically. Arrhythmia can lead to stroke, heart failure, or sudden cardiac arrest. Individuals with different inherited cardiac conditions may present with the same type of arrhythmia.

Arrhythmia may present with or without cardiomyopathy, a disease of the heart muscle. Some individuals who have a genetic predisposition for a primary arrhythmia condition will only develop arrhythmia. Other individuals who have a genetic predisposition for a primary arrhythmia condition may develop chronic arrhythmia, which can lead to cardiomyopathy. Finally, some individuals who have a genetic predisposition for a primary cardiomyopathy condition may present with arrhythmia before cardiomyopathy is apparent.

The clinical sensitivity of this test is dependent on the patient’s underlying genetic condition. This test covers all of the common genetic causes of LQTS, SQTS, Brugada syndrome, CVPT, and ARVC. For each condition, the chart below shows the percentage of clinical cases in which a pathogenic variant is expected to be identified through analysis of the genes on this panel.

Clinical sensitivity by underlying condition
50% 15%-30% 65% 70% Unknown

Most inherited arrhythmia disorders exhibit an autosomal dominant inheritance pattern. A small number of arrhythmias, such as LQTS due to Jervell and Lange-Nielsen syndrome (JLNS), CASQ2- related CPVT, TRDN-related arrhythmia, ARVC due to Naxos disease, or dilated cardiomyopathy due to Carvajal syndrome, are inherited in an autosomal recessive manner. EMD-related muscular dystrophy and variants in the candidate gene KCNE5 are inherited in an X-linked manner.

Most genetic forms of arrhythmia exhibit reduced penetrance, meaning not everyone who inherits a predisposition to develop arrhythmia will go on to manifest the disorder. Autosomal recessive Jervell and Lange-Nielsen syndrome, CASQ2-related CPVT, Naxos disease and Carvajal syndrome have higher penetrance, with most individuals developing signs and symptoms during their lifetime—often at young ages.

The chance to develop an arrhythmia typically increases with age. Individuals with a genetic predisposition to develop arrhythmia have an increased risk for arrhythmia at any age and frequently present with arrhythmia at younger ages compared to the general population. Symptoms are variable, even among affected members of the same family. Arrhythmia may occur spontaneously or be triggered by certain factors such as exercise, emotional stress, certain medications, fever, dehydration, or electrolyte imbalance.

Arrhythmia may also be the presenting feature of arrhythmogenic cardiomyopathy conditions. Individuals with a genetic predisposition to develop arrhythmogenic cardiomyopathy may initially have conduction disease, atrial fibrillation, ventricular tachycardia, or ventricular fibrillation, along with an increased risk to develop cardiomyopathy over the lifespan.

The prevalence of genetic forms of arrhythmia is dependent on the underlying condition.

ConditionEstimated prevalenceAdditional information
LQTS~1 in 2,000 
ARVC~1 in 2,000 to ~1:5,000Prevalence is increased in Italy and Greece, where it can be as high as 1 in 125 to 1 in 250.
CPVT~1 in 10,000 
BrugadaNo precise data availablePrevalence is much higher in Asian and Southeast Asian countries—especially Thailand, the Philippines, and Japan—and reaches 0.5–1 in 1,000 persons.

The specific prevalence of other inherited arrhythmias is unknown at this time.

This test may be considered for individuals with:

  • arrhythmia in the absence of clear structural heart disease
  • unexplained arrhythmia that may be consistent with multiple genetic arrhythmia conditions
  • unexplained sudden cardiac arrest

  1. Ackerman MJ, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). 2011 Heart Rhythm Aug; 8(8):1308-1339. PMID: 21787999
  2. Hsiao PY, et al. Gene mutations in cardiac arrhythmias: a review of recent evidence in ion channelopathies. 2013 Appl Clin Genet. Jan; 18 6:1-13. PMID: 23837003
  3. January CT, et al. AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. 2014 J Am Coll Cardiol. Dec; 2:64(21):e1-76. PMID: 24685669
  4. McNally, E, et al. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. 2005 Apr 18. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301310
  5. Mizusawa Y, et al. Genetics and clinical advances in congenital long QT syndrome. 2014 Circ J 78(12):2827-2833. PMID: 25274057
  6. NCBI GeneReviews. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.
  7. Nyegaard M, et al. Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. 2012 Am J Hum Genet. Oct; 91(4):703-712. PMID: 23040497
  8. Pinamonti B, et al. Arrhythmogenic right ventricular cardiomyopathy: From genetics to diagnostic and therapeutic challenges. 2014 World J Cardiol. Dec 26:6(12):1234-44. PMID: 25548613
  9. Priori, SG, et al. Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of individuals with inherited primary arrhythmia syndromes. 2013. Heart Rhythm, Dec;10(12):e85-108. PMID: 23916535
  10. Schwartz PJ, et al. Impact of genetics on the clinical management of channelopathies. 2013 J Am Coll Cardiol. Jul 16:62(3):169-180. PMID: 23684683
  11. Tester DJ, et al. Genetics of long QT syndrome. 2014 Methodist Debakey Cardiovasc J. Jan-Mar 10(1):29-33. PMID: 24932360

For links to published management guidelines for cardiology conditions, please refer to our Management guidelines page.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ABCC9 NM_005691.3
ACTN2 NM_001103.3
AKAP9 NM_005751.4
ANK2 NM_001148.4
ANKRD1* NM_014391.2
CACNA1C NM_000719.6
CACNA2D1 NM_000722.3
CACNB2 NM_201590.2
CALM1 NM_006888.4
CALM2 NM_001743.4
CALM3 NM_005184.2
CASQ2 NM_001232.3
CAV3 NM_033337.2
CTNNA3 NM_013266.3
DEPDC5 NM_001242896.1
DES NM_001927.3
DSC2 NM_024422.4
DSG2 NM_001943.3
DSP NM_004415.2
EMD NM_000117.2
GJA5 NM_005266.6
GPD1L NM_015141.3
HCN4 NM_005477.2
JUP NM_002230.2
KCNA5 NM_002234.3
KCND3 NM_004980.4
KCNE1 NM_000219.5
KCNE2 NM_172201.1
KCNE3 NM_005472.4
KCNE5 NM_012282.2
KCNH2 NM_000238.3, NM_172057.2
KCNJ2 NM_000891.2
KCNJ5 NM_000890.3
KCNJ8 NM_004982.3
KCNK3 NM_002246.2
KCNQ1 NM_000218.2
KCNQ2 NM_172107.2
KCNQ3 NM_004519.3
KCNT1* NM_020822.2
LDB3 NM_001080116.1, NM_001171610.1
LMNA NM_170707.3
MYL4 NM_001002841.1
NKX2-5 NM_004387.3
NPPA NM_006172.3
PCDH19 NM_001184880.1
PDLIM3 NM_014476.5
PKP2 NM_004572.3
PLN NM_002667.3
PRKAG2 NM_016203.3
PRRT2 NM_145239.2
RANGRF NM_016492.4
RBM20 NM_001134363.2
RYR2 NM_001035.2
SCN10A NM_006514.3
SCN1A NM_001165963.1
SCN1B NM_199037.3, NM_001037.4
SCN2B NM_004588.4
SCN3B NM_018400.3
SCN4B NM_174934.3
SCN5A NM_198056.2
SCN8A NM_014191.3
SCN9A NM_002977.3
SLC2A1 NM_006516.2
SLMAP NM_007159.2
SNTA1 NM_003098.2
TGFB3 NM_003239.3
TMEM43 NM_024334.2
TNNI3 NM_000363.4
TNNT2 NM_001001430.2, NM_000364.3
TRDN NM_006073.3
TRPM4 NM_017636.3
TTN* NM_001267550.2

ANKRD1: Deletion/duplication analysis is not offered for exons 3 or 4.
KCNT1: Deletion/duplication analysis is not offered for exons 26 or 27.
TTN: Deletion/duplication and sequencing analysis is not offered for exons 153-155 (NM_133378.4).