CustomNext-Cardio

CustomNext-Cardio is a gene sequencing and deletion/duplication panel that analyzes up to 106 genes of your choosing associated with inherited cardiomyopathies and arrhythmias, thoracic aortic aneurysms and dissections (TAAD), and other inherited cardiovascular conditions. 

PrintPrint

CustomNext-Cardio is a gene sequencing and deletion/duplication panel that analyzes up to 106 genes of your choosing associated with inherited cardiomyopathies and arrhythmias, thoracic aortic aneurysms and dissections (TAAD), and other inherited cardiovascular conditions. 

Ambry utilizes next generation sequencing (NGS) and deletion/duplication analyses (deletion/duplication for all genes except CBS, COL5A1, FLNATBX1, TXNRD2) to offer CustomNext-Cardio, a customizable hereditary cardiovascular panel of up to 106 genes. Gene options for this panel include any combination of genes included in the CardioNext and TAADNext panels: ABCC9, ACTA2, ACTC1, ACTN2, AKAP9, ANK2, ANKRD1, BAG3, CACNA1C, CACNA2D1, CACNB2, CALM1, CASQ2, CAV3, CBS, COL3A1, COL5A1, COL5A2, CRYAB, CSRP3, DES, DMD, DSC2, DSG2, DSP, EMD, EYA4, FBN1, FBN2, FKTN, FLNA, FXN, GATA4, GATAD1, GLA, GPD1L, HCN4, JAG1, JPH2, JUP, KCND3, KCNE1, KCNE2, KCNE3, KCNH2, KCNJ2, KCNJ5, KCNJ8, KCNQ1, LAMA4, LAMP2, LDB3/ZASP, LMNA, MED12, MYBPC3, MYH11, MYH6, MYH7, MYL2, MYL3, MYLK, MYOZ2, MYPN, NEXN, NKX2.5, NOTCH1, PKP2, PLN, PLOD1, PRKAG2, PRKG1, PTPN11, RAF1, RBM20, RYR2, SCN1B, SCN2B, SCN3B, SCN4B, SCN5A, SKI, SLC2A10, SMAD3, SMAD4, SNTA1, TAZ, TBX1, TBX20, TBX5, TCAP, TGFB2, TGFB3, TGFBR1, TGFBR2, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TRDN, TRPM4, TTN, TTR, TXNRD2, VCL.

Disease Name 
Arrhythmogenic right ventricular dysplasia (ARVD)
Arterial tortuosity syndrome
Brugada syndrome (BrS)
Catecholaminergic polymorphic ventricular tachycardia (CPVT)
Congenital contractural arachnodactyly (CCA or Beals syndrome)
Congenital heart defects
Dilated cardiomyopathy (DCM)
Ehlers-Danlos syndrome, vascular type (EDS IV)
Ehlers-Danlos syndrome, classic type (EDS I and II)
Familial thoracic aortic aneurysm and dissection (TAAD)
Homocystinuria caused by cystathionine beta-synthase deficiency
Hypertrophic cardiomyopathy (HCM)
Juvenile polyposis/Hereditary hemorrhagic telangiectasia syndrome (JPHT)
Left ventricular non-compaction (LVNC)
Loeys-Dietz syndrome, types 1-5
Long QT syndrome (LQTS)
Lujan-Fryns syndrome
Marfan syndrome (MFS)
Restrictive cardiomyopathy
Short QT syndrome (SQTS)
Shprintzen-Goldberg syndrome
X-linked periventricular nodular heterotopia, EDS variant
Disease Information 

CustomNext-Cardio has 106 genes to choose from, which includes all of the genes on the CardioNext and TAADNext panels.

Testing Benefits & Indication 

CustomNext-Cardio may be appropriate to consider in the following situations, combined with clinician discretion:

  • Clarify diagnosis and risk for sudden cardiac arrest or aortic aneurysms/dissections
  • Target medical management and prevention of cardiac arrest, aortic aneurysms/dissections, and other complications
  • Adjust management in those with cardiomyopathy due to a specific cardiac genotype, or underlying conditions like Duchenne muscular dystrophy and Danon disease
  • Indicated in patients who are clinically suspected to have MFS, Marfan syndrome-related disorders, or familial TAAD
  • May identify the cause of a sudden unexplained death after a normal autopsy
  • 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
  • Your patient's complex personal and and/or family history requires a unique panel of genes to assess (not found in an existing panel)
  • You/your patient would like to learn about fewer genes than those currently found on existing panels
  • You/your patient would like to learn about more genes than those currently found on existing panels
Test Description 

CustomNext-Cardio analyzes up to 106 genes (listed above) selected by the healthcare provider that cause inherited cardiomyopathies, inherited arrhythmias, and other inherited cardiovascular conditions. All selected genes are evaluated by NGS or Sanger sequencing of all coding domains, and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. 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. Additional Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection.  Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing. Gross deletion/duplication analysis is performed for the covered exons and untranslated regions of all ordered genes (excluding CBS, COL5A1, FLNA, TBX1 and TXNRD2) utilizing a targeted chromosomal microarray.

Mutation Detection Rate 

~65% of patients with LQTS; 50% of patients with HCM, ARVD or CPVT; 30% of patients with non-ischemic DCM; and 15-30% of patients with BrS have a mutation in one of the genes found in the CardioNext panel, which are available to order on the CustomNext-Cardio panel (clinical sensitivity). Up to 93% of patients with Marfan syndrome have a mutation in the FBN1 gene. >95% of patients with EDS type IV have a mutation in the COL3A1 gene. 30-40% of patients with familial TAAD have a mutation in one of the genes found on the TAADNext panel, which are available to order on the CustomNext-Cardio panel (clinical sensitivity). Many of these genes have very recently been identified, so this detection rate may increase as studies continue. CustomNext-Cardio can detect >99.9% of described sequencing and deletion/duplication mutations in the included genes listed above, 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)
9520 CustomNext-Cardio 4-5

 

Specialty 
Genes 
ABCC9
ACTA2
ACTC1
ACTN2
AKAP9
ANKRD1
ANK2
BAG3
CACNA1C
CACNA2D1
CACNB2
CALM1
CASQ2
CAV3
CBS
COL3A1
COL5A1
COL5A2
CRYAB
CSRP3
DES
DMD
DSC2
DSG2
DSP
EMD
EYA4
FBN1
FBN2
FLNA
FKTN
FXN
GATAD1
GATA4
GLA
GPD1L
HCN4
JAG1
JPH2
JUP
KCND3
KCNE1
KCNE2
KCNE3
KCNH2
KCNJ2
KCNJ5
KCNJ8
KCNQ1
LAMA4
LAMP2
LDB3/ZASP
LMNA
MED12
MYBPC3
MYH6
MYH7
MYH11
MYL2
MYL3
MYLK
MYPN
MYOZ2
NEXN
NKX2.5
NOTCH1
PKP2
PLN
PLOD1
PRKAG2
PRKG1
PTPN11
RAF1
RBM20
RYR2
SCN1B
SCN2B
SCN3B
SCN4B
SCN5A
SKI
SLC2A10
SMAD3
SMAD4
SNTA1
TAZ
TBX1
TBX5
TBX20
TCAP
TGFB2
TGFB3
TGFBR1
TGFBR2
TMEM43
TMPO
TNNC1
TNNI3
TNNT2
TPM1
TRDN
TRPM4
TTN
TTR
TXNRD2
VCL
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. Alders M, Mannens MMAM. Romano-Ward Syndrome. 2003 Feb 20 [Updated 2012 May 31]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. 
  6. Brugada R, Campuzano O, Brugada P et al. Brugada Syndrome. 2005 Mar 31 [Updated 2014 Apr 10]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. 
  7. Napolitano C, Priori SG, Bloise R. Catecholaminergic Polymorphic Ventricular Tachycardia. 2004 Oct 14 [Updated 2014 Mar 6]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. 
  8. 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.
  9. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.