CMNext

CMNextTM is a multi-gene panel for patients with inherited cardiomyopathy. Mutations in several genes are associated with different cardiomyopathy types. Given the genetic and clinical overlap between these conditions, one comprehensive inherited cardiomyopathy test may be the most effective way of identifying at-risk individuals, or confirming a diagnosis. 

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CMNextTM is a multi-gene panel for patients with inherited cardiomyopathy. Mutations in several genes are associated with different cardiomyopathy types. Given the genetic and clinical overlap between these conditions, one comprehensive inherited cardiomyopathy test may be the most effective way of identifying at-risk individuals, or confirming a diagnosis. 

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CMNext is a next generation sequencing (NGS) and deletion/duplication panel including 55 genes associated with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular dysplasia (ARVD), left ventricular non-compaction (LVNC), and/or restrictive cardiomyopathy. This panel also includes genes that can cause cardiomyopathy associated with inherited muscular dystrophies.  

Genes included in CMNext are: ABCC9, ACTC1, ACTN2, ANKRD1, BAG3, CRYAB, CSRP3, DES, DMD, DSC2, DSG2, DSP, EMD, EYA4, FKTN, FXN, GATAD1, GLA, JPH2, JUP, LAMA4, LAMP2, LDB3/ZASP, LMNA, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYOZ2, MYPN, NEXN, NKX2.5, PKP2, PLN, PRKAG2, PTPN11, RAF1, RBM20, RYR2, SCN5A, TAZ, TBX20, TCAP, TGFB3, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTR, TXNRD2, and VCL. These genes are also included in the comprehensive cardiovascular genetics (CardioNext) panel.

INHERITED CARDIMYOPATHY CLINICAL DESCRIPTION

Arrhythmogenic right ventricular dysplasia (ARVD)*

Progressive fibrofatty replacement of the myocardium in the right ventricle
Dilated cardiomyopathy (DCM) Left ventricular enlargement, with normal wall thickness and systolic dysfunction
Hypertrophic cardiomyopathy (HCM) Left ventricular hypertrophy, myocyte disarray, and fibrosis
Left ventricular non-compaction (LVNC) Excessive and unusual trabeculations within the mature
left ventricle

*Also known as ARVC: Arrhythmogenic right ventricular cardiomyopathy

 

Genes Implicated in Inherited Cardiomyopathy

51 genes implicated in inherited cardiomyopathy

 

Including the TTN Gene is Optional
Clinicians may also include the TTN gene in CMNext. TTN mutations account for up to 20% of all inherited DCM. However, the role of TTN in other forms of cardiomyopathy remains unclear. TTN is a very large gene, thus TTN testing is more likely than other genes to identify variants of uncertain significance (VUS), which may or may not contribute to the cardiomyopathy in a patient.

 

Disease Name 
Arrhythmogenic right ventricular dysplasia (ARVD)
Dilated cardiomyopathy (DCM)
Hypertrophic cardiomyopathy (HCM)
Left ventricular non-compaction (LVNC)
Restrictive cardiomyopathy
Testing Benefits & Indication 
  • Clarify diagnosis and risk for sudden cardiac arrest
  • Target medical management and prevention of cardiac arrest and other complications
  • Offer family members genetic testing (for a familial mutation) and implement medical surveillance to only those that need it
  • Reduce healthcare costs, resources, and anxiety for families
Test Description 

CMNext includes 55 genes that cause cardiomyopathy (listed earlier). Clinicians must choose whether or not to include TTN.  These genes are also included in the comprehensive cardiovascular genetics (CardioNext) panel. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, followed by polymerase chain reaction (PCR) and NGS. Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Suspect variant calls are verified by Sanger sequencing.  This assay targets all coding domains, and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. Gross deletion/duplication analysis for available genes is performed utilizing a targeted chromosomal microarray for 54 genes (all exceptTXNRD2).

Mutation Detection Rate 

~50% of patients with HCM or ARVD and about 30% of patients with non-ischemic DCM have a mutation in one of the CMNext genes (clinical sensitivity).  CMNext can detect >99.9% of described mutations in the included genes, when present (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above on this page.

Turnaround Time 
TEST CODE TEST NAME TURNAROUND TIME (Weeks)
8886 CMNext 4-5
8887 CMNext + TTN 4-5 
9520 CustomNext-Cardio
Up to 85 cardiovascular genes of your choice
4-5 weeks

 

Specialty 
Genes 
ABCC9
ACTC1
ACTN2
ANKRD1
BAG3
CRYAB
CSRP3
DES
DMD
DSC2
DSG2
DSP
EMD
EYA4
FKTN
FXN
GATAD1
JPH2
JUP
LAMA4
LAMP2
LDB3/ZASP
LMNA
MYBPC3
MYH6
MYH7
MYL2
MYL3
MYOZ2
MYPN
NEXN
NKX2.5
PKP2
PLN
PRKAG2
PTPN11
RAF1
RBM20
RYR2
SCN5A
TAZ
TBX20
TCAP
TGFB3
TMEM43
TMPO
TNNC1
TNNI3
TNNT2
TPM1
TTN
TTR
TXNRD2
VCL
GLA
Tests 
References 

1. Adapted from Ackerman MJ et al. HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies. Heart Rhythm. 2011 Aug;8(8):1308-39. 

2. Cirino AL, Ho C. Hypertrophic Cardiomyopathy Overview. 2008 Aug 5 [Updated 2014 Jan 16]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. 

3. Hershberger RE, Morales A. Dilated Cardiomyopathy Overview. 2007 Jul 27 [Updated 2013 May 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. 

4. McNally E, MacLeod H, Dellefave-Castillo L. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. 2005 Apr 18 [Updated 2014 Jan 9]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. 

5. Brodt C et al. Temporal relationship of conduction system disease and ventricular dysfunction in LMNA cardiomyopathy. J Card Fail. 2013. Apr;19(4):233-9.