163 genes sequenced: A2ML1, ABCC9, ACADVL, ACTA1, ACTA2, ACTC1, ACTN2, AGL, AKAP9, ALMS1, ALPK3, ANK2, ANKRD1, BAG3, BRAF, CACNA1C, CACNA2D1, CACNB2, CALM1, CALM2, CALM3, CALR3, CASQ2, CAV3, CBL, CHRM2, COL3A1, COL5A2, CPT2, CRYAB, CSRP3, CTF1, CTNNA3, DES, DMD, DNAJC19, DOLK, DSC2, DSG2, DSP, DTNA, EFEMP2, ELAC2, EMD, EYA4, FBN1, FBN2, FHL1, FHL2, FKRP, FKTN, FLNC, GAA, GATA4, GATA6, GATAD1, GLA, GPD1L, HCN4, HFE, HRAS, ILK, JPH2, JUP, KCND3, KCNE1, KCNE2, KCNE3, KCNE5 (KCNE1L), KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1, KRAS, LAMA4, LAMP2, LDB3, LMNA, LOX, LRRC10, MAP2K1, MAP2K2, MIB1, MTO1, MURC (CAVIN4), MYBPC3, MYH6, MYH7, MYH11, MYL2, MYL3, MYLK, MYLK2, MYOM1, MYOZ2, MYPN, NEBL, NEXN, NF1, NKX2-5, NOTCH1, NPPA, NRAS, PDLIM3, PKP2, PLEKHM2, PLN, PRDM16, PRKAG2, PTPN11, RAF1, RANGRF, RASA1, RBM20, RIT1, RRAS, RYR1, RYR2, SCN1B, SCN2B, SCN3B, SCN4B, SCN5A, SCN10A, SDHA, SEPN1 (SELENON), SGCD, SGCG, SHOC2, SLC22A5, SCL25A4, SLC2A10, SLMAP, SMAD3, SMAD4, SNTA1, SOS1, SOS2, SPRED1, TAZ, TBX20, TCAP, TGFB2, TGFB3, TGFBR1, TGFBR2, TMEM43, TMEM70, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TRDN, TRIM63, TRPM4, TTN, TTR, TXNRD2, VCL, YWHAE and ZBTB17.
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.
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) as well as thoracic aneurysm and aortic dissection.
Available Tests and Gene Lists
Comprehensive Cardiovascular Gene Set
Comprehensive Arrhythmia Gene Set
35 genes sequenced: AKAP9, ANK2, CACNA1C, CACNA2D1, CACNB2, CALM1, CALM2, CALM3, CASQ2, CAV3, GPD1L, HCN4, KCND3, KCNE1, KCNE2, KCNE3, KCNE5, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1, PKP2, RANGRF, RYR2, SCN1B, SCN2B, SCN3B, SCN4B, SCN5A, SCN10A, SLMAP, SNTA1, TRDN and TRPM4.
Brugada Syndrome (BrS)
18 genes sequenced: CACNA1C, CACNA2D1, CACNB2, GPD1L, HCN4, KCND3, KCNE3, KCNE5 (KCNE1L), KCNJ8, PKP2, RANGRF, SCN1B, SCN2B, SCN3B, SCN5A, SCN10A, SLMAP and TRPM4.
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
8 genes sequenced: ANK2, CALM1, CALM2, CALM3, CASQ2, KCNJ2, RYR2 and TRDN.
Long QT Syndrome (LQTS)
16 genes sequenced: AKAP9, ANK2, CACNA1C, CALM2, CALM3, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNQ1, SCN4B, SCN5A, SNTA1 and TRDN.
Short QT Syndrome (SQTS)
6 genes sequenced: CACNA1C, CACNA2D1, CACNB2, KCNH2, KCNJ2 and KCNQ1.
Comprehensive Cardiomyopathy Gene Set
115 genes sequenced: A2ML1, ABCC9, ACADVL, ACTA1, ACTC1, ACTN2, AGL, ALMS1, ALPK3, ANKRD1, BAG3, BRAF, CALR3, CASQ2, CBL, CHRM2, CPT2, CRYAB, CSRP3, CTF1, CTNNA3, DES, DMD, DNAJC19, DOLK, DSC2, DSG2, DSP, DTNA, ELAC2, EMD, EYA4, FHL1, FHL2, FKRP, FKTN, FLNC, GAA, GATA4, GATA6, GATAD1, GLA, HFE, HRAS, ILK, JPH2, JUP, KRAS, LAMA4, LAMP2, LDB3, LMNA, LRRC10, MAP2K1, MAP2K2, MIB1, MTO1, MURC (CAVIN4), MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYOM1, MYOZ2, MYPN, NEBL, NEXN, NF1, NKX2-5, NPPA, NRAS, PDLIM3, PKP2, PLEKHM2, PLN, PRDM16, PRKAG2, PTPN11, RAF1, RASA1, RBM20, RIT1, RRAS, RYR1, RYR2, SCN5A, SDHA, SEPN1 (SELENON), SGCD, SGCG, SHOC2, SLC22A5, SLC25A4, SOS1, SOS2, SPRED1, TAZ, TBX20, TCAP, TMEM43, TMEM70, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TRIM63, TTN, TTR, TXNRD2, VCL, YWHAE and ZBTB17.
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
11 genes sequenced: CTNNA3, DES, DSC2, DSG2, DSP, JUP, PDLIM3, PKP2, RYR1, RYR2 and TMEM43.
Dilated Cardiomyopathy (DCM)
67 genes sequenced: ABCC9, ACADVL, ACTA1, ACTC1, ACTN2, ALMS1, ALPK3, ANKRD1, BAG3, CBL, CHRM2, CPT2, CRYAB, CSRP3, CTF1, DES, DMD, DNAJC19, DOLK, EMD, EYA4, FHL1, FHL2, FKRP, FKTN, FLNC, GATA4, GATA6, GATAD1, HFE, ILK, LAMP2, LDB3, LMNA, LRRC10, MURC (CAVIN4), MYBPC3, MYH6, MYH7, MYPN, NEBL, NEXN, NKX2-5, NPPA, PDLIM3, PLEKHM2, PLN, RBM20, SCN5A, SDHA, SEPN1 (SELENON), SGCD, SGCG, SLC22A5, TAZ, TBX20, TCAP, TMEM70, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TXNRD2, VCL and ZBTB17.
Hypertrophic Cardiomyopathy (HCM)
62 genes sequenced: A2ML1, ACADVL, ACTA1, ACTC1, ACTN2, AGL, ALPK3, BRAF, CALR3, CBL, CPT2, CRYAB, CSRP3, ELAC2, FLNC, GAA, GATA4, GLA, HFE, HRAS, JPH2, KRAS, LAMP2, MAP2K1, MAP2K2, MTO1, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYOM1, MYOZ2, MYPN, NEXN, NF1, NPPA, NRAS, PDLIM3, PLN, PRKAG2, PTPN11, RAF1, RASA1, RIT1, RRAS, SEPN1 (SELENON), SGCG, SHOC2, SLC22A5, SLC25A4, SOS1, SOS2, SPRED1, TNNC1, TNNI3, TNNT2, TPM1, TRIM63, TTR and ZBTB17.
Left Ventricular Noncompaction (LVNC)
15 genes sequenced: ACTC1, CASQ2, DNAJC19, DTNA, LAMA4, LDB3, LMNA, MIB1, MYBPC3, MYH7, PRDM16, TAZ, TNNT2, VCL and YWHAE.
Thoracic Aortic Aneurysm and Dissection Gene Set
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).
For some cases with negative results or isolated heterozygous mutations in recessive genes, additional testing by alternate methodology may be performed to determine the presence of rare variant types not detected by this assay.
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 or 2-4 buccal swabs (please call the laboratory before sending buccal swabs). Specimen collection kits are available upon request.
***Already extracted DNA can be accepted only with laboratory approval. The isolation of nucleic acids for clinical testing must have occurred in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or the CMS.
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.