HCMFirst and HCMNext

HCMFirstTM and HCMNextTM are multi-gene panels that can be ordered individually or on a reflex basis for patients with hypertrophic cardiomyopathy (HCM). Often, HCM can be asymptomatic and sudden death is the first and only symptom. Therefore, genetic testing may be the most effective way of identifying at-risk individuals, or confirming a diagnosis.

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HCMFirstTM and HCMNextTM are multi-gene panels that can be ordered individually or on a reflex basis for patients with hypertrophic cardiomyopathy (HCM). Often, HCM can be asymptomatic and sudden death is the first and only symptom. Therefore, genetic testing may be the most effective way of identifying at-risk individuals, or confirming a diagnosis.

HCMFirst is a panel including the two genes most commonly associated with HCM: MYBPC3 and MYH7. These genes are implicated in over 80% of known genetic causes of HCM, so HCMFirst is an excellent first-tier testing option. HCMNext is a panel including 27 genes associated with HCM: ACTC1, ACTN2, ANKRD1, CSRP3, FXN, GLA, JPH2, LAMP2, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYOZ2, MYPN, NEXN, PLN, PRKAG2, PTPN11, RAF1, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTR and VCL. These genes are also included in the comprehensive inherited cardiomyopathy (CMNextTM) and cardiovascular genetics (CardioNextTM) panels. All panels are next generation sequencing (NGS) and deletion/duplication panels.  

Disease Name 
Hypertrophic cardiomyopathy (HCM)
Disease Information 

HCM occurs in approximately 1 in 500 individuals worldwide and is characterized by left ventricular hypertrophy, myocyte disarray, and fibrosis.  Severity ranges from asymptomatic left-ventricular hypertrophy to progressive heart failure or sudden cardiac death, and can vary widely within the same family. Age of onset is childhood to early adulthood. Inherited HCM follows an autosomal dominant pattern.

Management for HCM typically includes echocardiograms, electrocardiograms, and assessment for sudden cardiac death risk. Medical treatment to reduce hemodynamic stress is common. Implantable cardioverter defibrillator (ICD) or pacemaker placement may be recommended if arrhythmias are not well controlled, or if a patient is at high risk of sudden cardiac death.  HCM may present in childhood; treatment can be considered in children and adults with a high risk for HCM.  Heart transplantation may be necessary in those that develop end-stage heart failure.

Genetic Testing for Hypertrophic Cardiomyopathy

percent of patients that hcmfirst hcmnext will identify an inherited mutation that are diagnosed with hcm

Up to 50% of all patients with HCM have a mutation in one of the HCMFirst genes, which represent about 80% of known genetic causes of HCM. An additional 10% of patients with HCM may have a mutation in one of the HCMNext genes. 

Testing Benefits & Indication 
  • Clarify diagnosis and risk for sudden cardiac arrest
  • Target medical management and prevention of cardiac arrest and other complications
  • Confirm diagnosis and identify inherited mutation following a sudden death with autopsy findings that indicate HCM.
  • Adjust management in those with HCM due to conditions like Danon and Fabry diseases
  • 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 

HCMFirst includes two genes most commonly associated with inherited HCM: MYBPC3 and MYH7. HCMNext includes 27 genes that cause HCM: ACTC1, ACTN2, ANKRD1, CSRP3, FXN, GLA, JPH2, LAMP2, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYOZ2, MYPN, NEXN, PLN, PRKAG2, PTPN11, RAF1, TCAP, TNNC1, TNNI3, TNNT2, TPM1, TTR and VCL. These genes are also included in the comprehensive inherited cardiomyopathy (CMNext) and cardiovascular genetics (CardioNext) panels. 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 all 27 genes is performed utilizing a targeted chromosomal microarray. 

Mutation Detection Rate 

Up to 50% of all patients with HCM have a mutation in one of the HCMFirst genes, which represents about 80% of known genetic causes of HCM (clinical sensitivity).  An additional 10% of patients with HCM have a mutation in one of the HCMNext genes (clinical sensitivity).  HCMFirst and HCMNext will find >99% 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)
8935 HCMFirst  2-3 
8936 HCMNext 4-5 
8883 HCMFirst with automatic reflex to HCMNext 4-5 
8886 CMNext 4-5 
8887 CMNext + TTN 4-5 
8910 CardioNext 4-5 
8911 CardioNext + TTN 4-5 
9520 CustomNext-Cardio
Up to 85 cardiovascular genes of your choice
4-5 weeks

 

Specialty 
Genes 
ACTC1
ACTN2
ANKRD1
CSRP3
FXN
JPH2
LAMP2
MYBPC3
MYH6
MYH7
MYL2
MYL3
MYOZ2
MYPN
NEXN
PLN
PRKAG2
PTPN11
RAF1
TCAP
TNNC1
TNNI3
TNNT2
TPM1
TTR
VCL
GLA
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.