Cardiac Disease

Genomics and Pathology Services (GPS) offers germline variant detection by next-generation sequencing in key genes implicated in a variety of arrhythmias and cardiomyopathies.

Results can provide physicians with useful information to solidify a diagnosis, allowing for more appropriate patient management and surveillance. They also enable tailored genetic counseling in both the patient and at-risk family members.

REQUISITIONINFO SHEETGENES


Indications for Testing

Indications for testing include symptoms of a variety of arrhythmias and cardiomyopathies such as Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), short QT syndrome (SQTS), arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), Noonan syndrome and left ventricular noncompaction (LVNC).


Available Tests and Gene Lists

Comprehensive Cardiovascular Gene Set

80 genes sequenced include ABCC9, ACTC1, ACTN2, AKAP9, ANK2, ANKRD1, BAG3, BRAF, CACNA1C, CACNB2, CALM1, CASQ2, CAV3, CSRP3, CTF1, DES, DSC2, DSG2, DSP, DTNA, EMD, FHL1, FHL2, GATAD1, GLA, GPD1L, HCN4, HRAS, JUP, KCND3, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1, KRAS, LAMP2, LDB3, LMNA, MAP2K1, MAP2K2, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYOZ2, NEXN, NRAS, PKP2, PLN, PRKAG2, PTPN11, RAF1, RBM20, RIT1, RYR2, SCN1B, SCN3B, SCN4B, SCN5A, SGCD, SHOC2, SNTA1, SOS1, TAZ, TCAP, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR and VCL. 

Comprehensive Arrhythmia Gene Set

25 genes sequenced AKAP9, ANK2, CACNA1C, CACNB2, CALM1, CASQ2, CAV3, GPD1L, HCN4, KCND3, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1, RYR2, SCN1B, SCN3B, SCN4B, SCN5A and SNTA1.

Brugada Syndrome (BrS)

11 genes sequenced include CACNA1C, CACNB2, GPD1L, HCN4, KCND3, KCNE3, KCNJ8, PKP2, SCN1B, SCN3B and SCN5.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

5 genes sequenced include ANK2, CALM1, CASQ2, KCNJ2 and RYR2.

Long QT Syndrome (LQTS)

13 genes sequenced include AKAP9, ANK2, CACNA1C, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNQ1, SCN4B, SCN5A and SNTA1.

Short QT Syndrome (SQTS)

5 genes sequenced include CACNA1C, CACNB2, KCNH2, KCNJ2 and KCNQ1.

Comprehensive Cardiomyopathy Gene Set

59 genes sequenced include ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, BRAF, CASQ2, CSRP3, CTF1, DES, DSC2, DSG2, DSP, DTNA, EMD, FHL1, FHL2, GATAD1, GLA, HRAS, JUP, KRAS, LAMP2, LDB3, LMNA, MAP2K1, MAP2K2, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYOZ2, NEXN, NRAS, PKP2, PLN, PRKAG2, PTPN11, RAF1, RBM20, RIT1, RYR2, SCN5A, SGCD, SHOC2, SOS1, TAZ, TCAP, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR and VCL. 

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

8 genes sequenced include DES, DSC2, DSG2, DSP, JUP, PKP2, RYR2 and TMEM43.

Dilated Cardiomyopathy (DCM)

32 genes sequenced include ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CSRP3, CTF1, DES, EMD, FHL1, FHL2, GATAD1, LAMP2, LDB3, LMNA, MYBPC3, MYH6, MYH7, NEXN, PLN, RBM20, SCN5A, SGCD, TAZ, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN and VCL.

Hypertrophic Cardiomyopathy (HCM)

31 genes sequenced include ACTC1, ACTN2, BRAF, CSRP3, GLA, HRAS, KRAS, LAMP2, MAP2K1, MAP2K2, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYOZ2, NEXN, NRAS, PLN, PRKAG2, PTPN11, RAF1, RIT1, SHOC2, SOS1, TNNC1, TNNI3, TNNT2, TPM1 and TTR.

Left Ventricular Noncompaction (LVNC)

10 genes sequenced include ACTC1, CASQ2, DTNA, LDB3, LMNA, MYBPC3, MYH7, TAZ, TNNT2 and VCL.


Testing Methodology

Tests are performed using targeted hybridization capture coupled with next-generation sequencing (NGS) in our CAP/CLIA labs for comprehensive coverage of all coding exons of ordered genes.

Types of variation detected include single nucleotide variants (SNVs) and small insertions and deletions (indels).


Results and Interpretation

DNA sequence data are analyzed by GPS’ clinically validated bioinformatics pipeline to identify and annotate genetic variants associated with the phenotype(s).

Variants are interpreted by a board-certified clinical genomicist in the context of the patient’s disease. Those that are most likely to account for the observed clinical phenotype based on evidence from the medical literature are highlighted.

Results are returned to the ordering physician in a concise report.

The turnaround time for testing and interpretation is four to six weeks from the time a specimen arrives.


Specimen Requirements

Specimen types accepted include 2-5 mL peripheral blood in a lavender-top EDTA tube. Specimen collection kits are available upon request.

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Clinical Utility

Genetic variation within a number of genes has now been described in association with cardiomyopathies and arrhythmias.

Determination of the underlying genetic cause of these heart disorders can aid in diagnosis and provide information of prognostic and therapeutic relevance.

Diagnosis – Observation of a known or expected pathogenic variant by genetic testing can solidify a clinical diagnosis allowing for appropriate patient management and surveillance and allows for screening of at-risk family members.

Prognosis – Genotype-phenotype relationships have been established in some forms of cardiac disease.

Knowledge of the causative genetic variant can provide information surrounding the genotype-specific natural history of the disease, response to pharmacotherapy, and symptom triggers.

Treatment – Therapeutic interventions exist for many forms of cardiac disease. Therapies may include drug or surgical interventions as appropriate for optimal patient management.

For example, use of beta blockers for management of patients with Long QT syndrome, or early, pre-emptive intervention with an implantable cardiac defibrillator may be advocated in patients with dilated cardiomyopathy.