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Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy via the ACTN2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4545 ACTN2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4545ACTN281479 81479(x2) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Chun-An Chen, PhD

Clinical Features and Genetics

Clinical Features

Hypertrophic cardiomyopathy (HCM) is a disease of the cardiac muscle characterized by idiopathic hypertrophy of the left ventricle without predisposing conditions, such as aortic stenosis or hypertension (Cirino et al. GeneReviews). Hypertrophy of the right ventricle may also occur occasionally (Fifer and Vlahakes. Circulation 117:429-439, 2008). HCM is distinguished by extensive clinical variability with regards to the age of onset, pattern and extent of hypertrophy, and prognosis, even within individuals of the same family. Symptoms include dyspnea, exercise intolerance, chest pain, palpitations, arrhythmia, atrial fibrillation, presyncope, syncope, and sudden death (Maron et al. N Engl J Med 316:780-789, 1987). Additional features include left ventricular outflow tract obstruction, which is associated with increased risk for heart failure and cardiovascular death if left untreated (Ommen et al. J Am Coll Cardiol 46:470-476, 2005; Agarwal et al. Am Coll Cardiol 55:823-834, 2010). HCM is most often diagnosed with 2D echocardiography but can also be diagnosed by the presence of myocyte disarray upon histological examination and through genetic testing. HCM affects 1 in 500 people worldwide (Maron et al. Circulation 92:785-789, 1995).

Idiopathic dilated cardiomyopathy (DCM) is a heterogeneous disease of the cardiac muscle. It is characterized by enlargement of the left ventricle, systolic dysfunction, and diminished myocardial contractility (Hershberger et al. GeneReviews). Symptoms include arrhythmia, dyspnea, chest pain, palpitation, fainting, and congestive heart failure (Ikram et al. Br Heart J 57:521-527, 1987). Sudden death occurs in ~30% of patients with DCM (Tamburro and Wilber Am Heart J 124:1035-1045, 1992). Although symptoms of DCM usually begin in adulthood, an extensive clinical variability between individuals concerning the age of onset, penetrance, and extent of structural and functional abnormalities has been documented. Familial DCM is diagnosed based on family history and genetic testing. The prevalence of DCM has been estimated at ~1 in 2700 individuals (Codd et al. Circulation 80:564-572, 1989).

Genetics

Familial HCM is inherited in an autosomal dominant manner caused by variants in genes that encode different components of the sarcomere. Defects in fourteen genes, including ACTN2 (Chiu et al. J Am Coll Cardiol 55:1127-1135, 2010), account for approximately 60% of all HCM cases. All documented causative variants in ACTN2 in patients with HCM are missense variants (Chiu et al. J Am Coll Cardiol 55:1127-1135, 2010). In addition to HCM, ACTN2 variants have been implicated in dilated cardiomyopathy (DCM). ACTN2-associated DCM is inherited in an autosomal dominant manner (Mohapatra et al. Mol Genet Metab 80:207-215, 2003; Zimmerman et al. Genet Med 12:268-278, 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

This test allows the detection of variants in ~2% of HCM patients (Chiu et al. J Am Coll Cardiol 55:1127-1135, 2010) and in less than 1% of patients with DCM (Hershberger et al. Circ Heart Fail 2:253-261, 2009).

Testing Strategy

This test provides full coverage of all coding exons of the ACTN2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with symptoms suggestive of HCM or DCM.

Gene

Official Gene Symbol OMIM ID
ACTN2 102573
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Dilated Cardiomyopathy 1Aa AD 612158

Related Tests

Name
Comprehensive Cardiology Panel
Sudden Cardiac Arrest Panel

Citations

  • Agarwal S, et al. (2010) "Updated meta-analysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy." J Am Coll Cardiol 55:823-834. PubMed ID: 20170823
  • Chiu, C., et.al. (2010). "Mutations in Alpha-Actinin-2 Cause Hypertrophic Cardiomyopathy A Genome-Wide Analysis." J Am Coll Cardiol. 55(11):1127-1135. PubMed ID: 20022194
  • Cirino, A.L., Ho, C. (2009). "Familial Hypertrophic Cardiomyopathy Overview." PubMed ID: 20301725
  • Codd MB. et al. 1989. Circulation. 80: 564-72. PubMed ID: 2766509
  • Fifer MA, Vlahakes GJ. 2008. Management of symptoms in hypertrophic cardiomyopathy. Circulation 117: 429-439. PubMed ID: 18212300
  • Hershberger RE, Cowan J, Morales A, Siegfried JD. 2009. Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ. Heart Fail. 2: 253-261. PubMed ID: 19808347
  • Hershberger, R. et.al. (2009). "Dilated Cardiomyopathy Overview." PubMed ID: 20301486
  • Ikram H. et al. 1987. British heart journal. 57: 521-7. PubMed ID: 3620228
  • Maron BJ, Bonow RO, Cannon RO 3rd, Leon MB, Epstein SE. 1987. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1). N. Engl. J. Med. 316: 780-789. PubMed ID: 3547130
  • Maron, B. J., et.al. (1995). "Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults." Circulation 92(4): 785-9. PubMed ID: 7641357
  • Mohapatra, B., et.al. (2003). "Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis." Mol Genet Metab 80(1-2): 207-15. PubMed ID: 14567970
  • Ommen SR, Maron BJ, Olivotto I, Maron MS, Cecchi F, Betocchi S, Gersh BJ, Ackerman MJ, McCully RB, Dearani JA, Schaff HV, Danielson GK, Tajik AJ, Nishimura RA. 2005. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 46: 470-476. PubMed ID: 16053960
  • Tamburro P., Wilber D. 1992. American heart journal. 124: 1035-45. PubMed ID: 1529877
  • Zimmerman, R. et al. (2010) "A novel custom resequencing array for dilated cardiomyopathy." Genet Med 12:268-278. PubMed ID: 20474083

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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