Hypertrophic Cardiomyopathy and Related Disorders via the ACTC1 Gene
Summary and Pricing
Test MethodExome Sequencing with CNV Detection
|Test Code||Test Copy Genes||Test CPT Code||Gene CPT Codes Copy CPT Codes||Base Price|
|8751||ACTC1||81405||81405,81479||$890||Order Options and Pricing|
|Test Code||Test Copy Genes||Test CPT Code||Gene CPT Codes Copy CPT Code||Base Price|
|8751||ACTC1||81405||81405, 81479||$890||Order Options and Pricing|
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.
The Sanger Sequencing method for this test is NY State approved.For Sanger Sequencing click here.
18 days on average for standard orders or 14 days on average for STAT orders.
Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
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).
Familial HCM is inherited in an autosomal dominant manner caused by mutations in genes that encode different components of the sarcomere. Defects in fourteen genes, including ACTC1 (Mogensen et al. J Clin Invest 103:R39-43, 1999), account for approximately 60% of all HCM cases. Mutations have been identified in both familial and sporadic cases, with similar distribution. Mutations identified in sporadic cases were either nonpenetrant in family members or arose de novo. Most documented causative mutations in ACTC1 in patients with HCM are missense mutations. In addition to HCM, ACTC1 mutations have been implicated in dilated cardiomyopathy (DCM) (Olson et al. Science 280:750-752, 1998), left ventricular noncompaction (LVNC) (Monserrat et al. Europ Heart J 28:1953-1961, 2007) childhood restrictive cardiomyopathy (RCM) (Kaski et al. Heart 94:1478-1484, 2008) and in patients with atrial septal defect (ASD5) (Matsson et al. Hum Mol Genet 17:256-265, 2008).
Clinical Sensitivity - Sequencing with CNV PGxome
ACTC1 pathogenic mutations are rare. Perhaps 1% of HCM patients with known causative mutations have mutations in ACTC1 (Hershberger et al. Circ Heart Fail 2:253-261, 2009). Less than 1% of patients with ASD5 have mutations in ACTC1 (Matsson et al. Hum Molec Genet 17:256-265, 2008).
This test provides full coverage of all coding exons of the ACTC1 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.
Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).
Indications for Test
Patients with symptoms suggestive of HCM , RCM, DCM, LVNC and ASD5.
Patients with symptoms suggestive of HCM , RCM, DCM, LVNC and ASD5.
|Official Gene Symbol||OMIM ID|
|Atrial Septal Defect 5||AD||612794|
|Dilated Cardiomyopathy 1R||AD||613424|
|Familial Hypertrophic Cardiomyopathy 11||AD||612098|
|Comprehensive Cardiology Panel|
|Left Ventricular Noncompaction (LVNC) Panel|
|Pan Cardiomyopathy Panel|
- 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
- Cirino, A.L., Ho, C. (2009). "Familial Hypertrophic Cardiomyopathy Overview." PubMed ID: 20301725
- 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
- Kaski, J. P., et.al. (2008). "Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes." Heart 94(11): 1478-84. PubMed ID: 18467357
- 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
- Matsson, H., et al. (2008). "Alpha-cardiac actin mutations produce atrial septal defects." Hum Molec Genet 17: 256-265. PubMed ID: 17947298
- Matsson, H., et.al. (2008). "Alpha-cardiac actin mutations produce atrial septal defects." Hum Mol Genet 17(2): 256-65.
- Mogensen, J., et.al. (1999). "Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy." J Clin Invest 103(10): R39-43. PubMed ID: 10330430
- Monserrat, L. et al. (2007) "Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects." Europ Heart J. 28:1953-1961. PubMed ID: 17611253
- Olson, T. M., et.al. (1998). "Actin mutations in dilated cardiomyopathy, a heritable form of heart failure." Science 280(5364): 750-2. PubMed ID: 9563954
- 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
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.
- 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.