Arrhythmia Panels

Starting on June 26, 2013, Ambry Genetics will no longer accept samples for some of its cardiovascular next generation sequencing (NGS) panels. Suspended panels include: Brugada syndrome, Long QT syndrome, Arrhythmia, DCM, HCM, Cardiomyopathy and Pan Cardio. We are offering TAADNext (NGS panel for Marfan syndrome, Aneurysms, and Related Disorders), and Familial Hypercholesterolemia testingIn the near future we plan to release updated, targeted cardiovascular NGS panels, with the addition of deletion/duplication analysis.

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Starting on June 26, 2013, Ambry Genetics will no longer accept samples for some of its cardiovascular next generation sequencing (NGS) panels. Suspended panels include: Brugada syndrome, Long QT syndrome, Arrhythmia, DCM, HCM, Cardiomyopathy and Pan Cardio. We are offering TAADNext (NGS panel for Marfan syndrome, Aneurysms, and Related Disorders), and Familial Hypercholesterolemia testingIn the near future we plan to release updated, targeted cardiovascular NGS panels, with the addition of deletion/duplication analysis.

Ambry utilizes next-generation sequencing to offer a 9-gene Brugada Syndrome Panel, a 12-gene Long QT Syndrome Panel and a 29-gene Arrhythmia Panel that incorporates genes implicated in LQTS, Brugada, catecholaminergic polymorphic ventricular tachycardia (CPVT) and several other arrhythmic disorders, as well as sudden cardiac arrest (SCA).

 

Disease Name 
Brugada syndrome (Brugada)
LongQT syndrome (LQTS)
Catecholaminergic polymorphic ventricular tachycardia (CPVT)
Short QT syndrome (SQTS)
Sudden cardiac arrest (SCA)
Laminopathies
LMNA- related conduction system disease
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)
Cardiac channelopathies
Disease Information 

Cardiac arrhythmia refers to a wide variety of conditions in which there is abnormal electrical activity in the heart. Currently, more than 29 genes have been implicated in various types of arrhythmias, including Long QT syndrome (LQTS), Brugada Syndrome (Brugada), catecholaminergic polymorphic ventricular tachycardia (CPVT) and atrial fibrillation. In addition, several cardiomyopathies, including ARVD/C and LMNA-related dilated cardiomyopathy, can present with arrhythmia alone or sudden cardiac death.

Many different genetic causes of arrhythmia have been discovered. Identifying an underlying genetic diagnosis for arrhythmias can influence medical management decisions and preventive screening options for at-risk relatives. Careful consideration of the personal and family history should be considered when deciding which arrhythmia panel is most appropriate for testing in an individual patient or family.

Brugada Syndrome Panel
Brugada syndrome is characterized by right precordial ST wave elevation. Positive family history for sudden premature death and potentially lethal arrhythmias are also common. The prevalence of Brugada syndrome is 1/5000 to 1/10,000 in Western countries with a higher prevalence in South Asia. At least eight genes have been implicated in the disorder, which demonstrates an autosomal dominant pattern of inheritance. Variations in the most commonly mutated gene in Brugada Syndrome, SCN5A (sodium channel, voltage-gated, type V, alpha subunit), account for 15-30% of cases. 

Genes that have been implicated in Brugada syndrome are included on Ambry’s Brugada Syndrome Panel (9 genes). They can also be ordered as part of Ambry’s Arrhythmia Panel (29 genes) or Pan Cardio Panel (79 genes). For a comparison of all genes by panel, please click here.

Long QT Syndrome (LQTS) Panel
LQTS is characterized by prolonged QT and T-wave abnormalities, ventricular tachycardia and syncope (fainting). Young patients may often be asymptomatic and suddenly suffer cardiac death. The estimated incidence of Long QT Syndrome is 1/2500. The majority of cases are inherited as an autosomal dominant condition known as Romano-Ward syndrome. An autosomal recessive form known as Jervell and Lange-Nielsen syndrome is estimated to affect less than 1/1,000,000 individuals. At least 12 genes have been implicated in long QT syndrome, the majority of which encode proteins that make up sodium or potassium channels. The two most commonly mutated genes, potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) and potassium voltage-gated channel, subfamily H, member 2 (KCNH2) account for 58% and 35% of cases with a known genetic cause, respectively. Genes that have been implicated in LQTS are included on Ambry’s Long QT Syndrome Panel (12 genes). They can also be ordered as part of Ambry’s Arrhythmia Panel (29 genes) or Pan Cardio Panel (79 genes). For a comparison of all genes by panel, please click here.

Arrhythmia Panel
There can be significant overlap in genetic causes between different subtypes of arrhythmias.   In addition, clinical symptoms can also overlap. and several cardiomyopathies, including ARVD/C and LMNA-related dilated cardiomyopathy can present as arrhythmia or sudden cardiac death. While there are specific clinical distinctions between each subclass of arrhythmias, this level of detail is not always available to a clinician, particularly for family members of a proband. In any of these scenarios, the 29-gene Arrhythmia Panel may provide supporting diagnostic evidence regarding the underlying cause of disease.

Test Description 

Ambry's Long QT, Brugada, and Arrhythmia Panels target detection of mutations in 12, 9, and 29 genes, respectively, by next-generation sequencing of all coding exons plus at least 5 bases into the 5’ and 3’ ends of all the introns.

Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified by agarose gel electrophoresis. Sequence enrichment is carried out by incorporating the gDNA into microdroplets along with primer pairs designed to the target gene coding exons followed by polymerase chain reaction (PCR) and next-generation sequencing. Additional Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Suspect variant calls other than those classified as "likely benign" or "benign" are verified by sanger sequencing in sense and antisense directions. 


LongQT Syndrome Panel Gene List: AKAP9, ANK2, CACNA1C, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, SCN4B, SCN5A, SNTA1

Brugada Syndrome Panel Gene List: CACNA1C, CACNA2D1, CACNB2, GPD1L, KCNE3, KCNJ8, SCN1B, SCN3B, SCN5A

Arrhythmia Panel Gene List: AKAP9, ANK2, CACNA1C, CACNA2D1, CACNB2, CASQ2, CAV3, DES, DSC2, DSG2, DSP, GPD1L, JUP, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ8, KCNQ1, LMNA, PKP2, RYR2, SCN1B, SCN3B, SCN4B, SCN5A, SNTA1, TMEM43
 

Mutation Detection Rate 

The average analytical sensitivity across all genes is >97% of described mutations.

Specimen Requirements 

Blood: 6-10 cc blood in purple top EDTA tube (preferred) or yellow top citric acetate tube.
Store at 2-8°C. Do not freeze.
Ship at Room temperature for two-day delivery.

DNA: 20 μg of of DNA in TE (10mM Tris-Cl pH 8.0, 1mM EDTA);
Preferred at ~200 ng/μl.
Please provide DNA with OD 260:280 ratio (preferred 1.7-1.9) and send agarose picture with high-molecular-weight genomic DNA, if available.
Storage at -20°C.
Ship frozen on dry ice is preferred, or ship on ice

*NOTE: Saliva not accepted for these tests at this time.

Turnaround Time 
Technique Weeks
Arrhythmia Panel 12-16
Long QT Syndrome Panel 12-16
Brugada Syndrome Panel

12-16

 

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