Cardiomyopathy Panels

Starting on June 26, 2013, Ambry Genetics will no longer accept cardiovascular NGS panels for testing. Suspended tests include: Brugada syndrome, Long QT syndrome, Arrhythmia, DCM, HCM, Cardiomyopathy and Pan Cardio panels. We will still be offering testing for Marfan, Aneurysm and Related Disorders, and Familial HypercholesterolemiaIn the future, we plan to release updated versions of cardiovascular NGS panels for testing with the addition of deletion/duplication analysis.

Ambry Genetics offers gene sequencing panels for several different types of cardiomyopathy that can have a genetic cause, including dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Ambry also offers a large panel that encompasses genes implicated in HCM, DCM and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). 

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Starting on June 26, 2013, Ambry Genetics will no longer accept cardiovascular NGS panels for testing. Suspended tests include: Brugada syndrome, Long QT syndrome, Arrhythmia, DCM, HCM, Cardiomyopathy and Pan Cardio panels. We will still be offering testing for Marfan, Aneurysm and Related Disorders, and Familial HypercholesterolemiaIn the future, we plan to release updated versions of cardiovascular NGS panels for testing with the addition of deletion/duplication analysis.

Ambry Genetics offers gene sequencing panels for several different types of cardiomyopathy that can have a genetic cause, including dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Ambry also offers a large panel that encompasses genes implicated in HCM, DCM and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). 

Ambry utilizes next generation sequencing to offer a 31-gene HCM panel, a 37-gene DCM panel and a 56-gene cardiomyopathy panel, which includes genes implicated in DCM, HCM and ARVD/C.

Disease Name 
Hypertrophic Cardiomyopathy (HCM)
Dilated Cardiomyopathy (DCM)
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C)
Disease Information 

Cardiomyopathies, or heart muscle diseases, are a common cause of heart failure, which is a leading cause of death in the United States. There are several different types of cardiomyopathy, many of which can have a hereditary cause. Different types of cardiomyopathy can include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C).

Many different genetic causes of cardiomyopathy have been discovered. Identifying an underlying genetic diagnosis for a cardiomyopathy 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 cardiomyopathy panel is most appropriate for testing in an individual patient or family.

HCM Panel
Hypertrophic cardiomyopathy (HCM) has an estimated prevalence of 1/500 and is characterized by left ventricular hypertrophy (LVH), myocyte disarray and fibrosis. Age of onset ranges from childhood to early adulthood. Mutations in over 30 genes have been implicated in HCM with mutations in MYH7 and MYBPC3 accounting for 60-80% known genetic cause. Genes implicated in HCM primarily encode sarcomeric proteins. Syndromic and non-syndromic genetic forms of HCM have been observed, and in approximately 2-5% of cases, multiple mutations have been observed. Genes that have been implicated in HCM are included on Ambry’s HCM Panel (31 genes). They can also be ordered as part of Ambry’s Cardiomyopathy Panel (56 genes) or Pan-Cardio Panel (79 genes).  For a comparison of genes offered by panel, please see the table here.

DCM Panel
Dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement (LVE) with normal wall thickness and systolic dysfunction with an ejection fraction (EF) less than 45-50%. The prevalence of DCM is estimated to be ~1/2700, though this may be a gross underestimate.  Ischemic heart disease is the most common cause of DCM, accounting approximately half of all cases. Of the remaining non-ischemic DCM cases, approximately 20-35% of cases present with a family history. Genetic causes have been identified in familial and sporadic forms of non-ischemic dilated cardiomyopathy, with more than 40 genes implicated in hereditary causes of DCM. Mutations in three genes (LMNA, MYH7, and TNNT2) have been identified in at least 12-20% of cases with mutations in an additional 30-35 genes cumulatively accounting for another ~10-20% of genetic cause, including genes that encode sarcomeric, nuclear, cytoskeletal-membrane, z-disk and mitochondrial proteins.

Mutations in the majority of genes associated with DCM are nonsyndromic, although several genes on this panel can also be associated with syndromic conditions. For example, alterations in the EMD gene can cause X-linked Emery-Dreifuss muscular dystrophy (EDMD), which is characterized by joint contractures, slowly progressive muscle weakness and cardiovascular involvement.  Genes that have been implicated in DCM are available in Ambry’s DCM Panel (37 genes). They can also be ordered as part of Ambry’s Cardiomyopathy Panel (56 genes) or Pan-Cardio Panel (79 genes). For a comparison of genes offered by panel, please see the table here.

Cardiomyopathy Panel
Determining the genetic cause of cardiomyopathies can be complex. There have been many different genes (> 55) and many different alterations (mutations) involved in inherited predisposition to cardiomyopathy. The genetic cause is further complicated because there is a lot of overlap in the way different types of cardiomyopathy can present and also significant overlap in the genetic causes between subtypes. For example, at least 19 genes have been implicated in both HCM and DCM, and occasionally a person who initially had HCM, may not be diagnosed with heart disease until the disease is very advanced and presents as DCM. Likewise, ARVD/C, another subtype of cardiomyopathy, can also present in late stages with DCM.

In addition, different types of cardiomyopathy can run in families. In some families you will see exclusively one type of cardiopmyopathy, such as HCM, whereas in another family you might see the same genetic alteration causing different types of cardiomyopathy in different family members, such as DCM and HCM. Due to this overlap in genetic causes and in the symptoms and presentation of disease for different types of cardiomyopathy, a clinician may consider testing for genes associated with multiple subtypes of cardiomyopathy in one comprehensive test.

Ambry’s Cardiomyopathy Panel (56 genes) includes genes that have been implicated in DCM, HCM and ARVD/C (ARVD/C is a subtype of cardiomyopathy that is characterized by right ventricular (RV) fibrofatty replacement, RV myocyte loss and RV wall thinning). These genes can also be ordered as part of Ambry’s Pan Cardio Panel (79 genes).
 

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a less common disease characterized by right ventricular (RV) fibrofatty replacement, RV myocyte loss and RV wall thinning. Approximately 30-50% of cases are thought to be familial and a genetic cause can identified in approximately 40-50% of cases. Mutations implicated in ARVD/C have been identified in eight genes, primarily encoding desmosomal proteins. 

Genes implicated in ARVD/C are included in Ambry’s Cardiomyopathy Panel, Arrhythmia Panel or Pan Cardio Panel. For a comparison of genes offered by panel, please see the table here.

Test Description 

The DCM, HCM, and cardiomyopathy panels target detection of mutations in 37, 31, and 56 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. 


DCM Panel Gene List: ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CRYAB, CSRP3, DES, DMD, EMD, EYA4, ILK, LAMP2, LDB3/ZASP, LMNA, MYBPC3, MYH6, MYH7, MYPN, NEBL, NEXN, PDLIM3, PLN, RBM20, SCN5A, SGCD, TAZ, TCAP, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, TXNRD2, VCL

HCM Panel Gene List: ACTC1, ACTN2, ANKRD1, CALR3, CAV3, CSRP3, DES, FXN, GLA, JPH2, LAMP2, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYOM1, MYOZ2, NEXN, PLN, PRKAG2, PTPN11, RAF1, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, VCL

Cardiomyopathy Panel Gene List: ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CALR3, CAV3, CRYAB, CSRP3, DES, DMD, DSC2, DSG2, DSP, EMD, EYA4, FXN, GLA, ILK, JPH2, JUP, LAMP2, LDB3/ZASP, LMNA, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYOM1, MYOZ2, MYPN, NEBL, NEXN, PDLIM3, PKP2, PLN, PRKAG2, PTPN11, RAF1, RBM20, RYR2, SCN5A, SGCD, TAZ, TCAP, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, TXNRD2, VCL

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

Saliva: Collect 2ml in Oragene Self Collection container
Storage: At room temperature in sterile bag.
Shipment: Ship room temperature for two-day deliver
*Note 2 Oragene Self Collection containers must be submitted for any of our Next-Generation sequencing panels (XLID, CancerNext, PanCardio etc.)

Billing Codes 
Test Code Technique
8852 Cardiomyopathy Panel
8844 DCM Panel
8846 HCM Panel

 

Turnaround Time 
Technique Weeks
Cardiomyopathy Panel 12-16
DCM Panel 12-16
HCM Panel 12-16

 

Specialty