Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy via the PLN Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 9233 | PLN | 81403 | 81403,81479 | $990 | 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 platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
Clinical Features and Genetics
Clinical Features
Dilated cardiomyopathy (DCM) is a heterogeneous disease of the heart muscle. It is characterized by dilatation of the left, right, or both ventricles; systolic dysfunction; and diminished myocardial contractility. Symptoms include arrhythmia, dyspnea, chest pain, palpitation, fainting, and congestive heart failure (Ikram et al. Br Heart J 57:521-527, 1987). Additional features may include woolly hair and myopathy (Moller et al. Eur J Hum Genet 17:1241-1249, 2009). 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, extensive clinical variability between individuals concerning the age of onset and extent of structural and functional abnormality has been documented. The prevalence of DCM has been estimated at ~1/2700 (Codd et al. Circulation 80:564-572, 1989).
Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle characterized by idiopathic hypertrophy of the left ventricle, although hypertrophy of the right ventricle may occur occasionally (Fifer and Vlahakes Circulation 117:429-439, 2008). HCM is distinguished by an extensive clinical variability between individuals with regards to the age of onset, pattern and extent of hypertrophy, and prognosis. Symptoms include dyspnea, exercise intolerance, chest pain, palpitations, arrhythmia, atrial fibrillation, 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 (Ommen et al. J Am Coll Cardiol 46:470-476, 2005). HCM affects 1 in 500 people worldwide (Maron et al. Circulation 92:785-789, 1995).
Genetics
Up to 30% of DCM cases are familial (Grunig et al. J Am Coll Cardiol 31:186-194, 1998). In about half of these families, DCM is inherited in an autosomal dominant manner (AD-DCM). Less commonly, the disease is transmitted with an autosomal recessive, X-linked, or mitochondrial inheritance. AD-DCM is caused by defects in 24 genes encoding myocardial proteins. One of these genes, PLN, encodes for a cardiac phospholamban, a transmembrane phosphoprotein expressed on the sacoplasmic reticulum membrane. PLN variants have been reported in patients with AD-DCM (Hershberger et al. J Cardiac Fail 15:83-97, 2009). PLN-associated DCM has incomplete penetrance (Haghighi et al. Hum Mutat 29:640-647, 2008). One missense variant, p.Arg9Cys, has been found to segregate in a 4-generation family with DCM (Schmitt et al. Science 299:1410-1413). In addition, a nonsense variant, p.Leu39*, has been identified in individuals with DCM and in individuals with hypertrophic cardiomyopathy (HCM) (Haghighi et al. Hum Mutat 29:640-647, 2008; Chiu et al. J Mol Cell Cardiol 43:337-343, 2007; Landstrom et al. Am Heart J 161:165-171, 2011).
Clinical Sensitivity - Sequencing with CNV PGxome
The incidence of PLN variants in DCM is unknown. Less than <1% of individuals with HCM have variants in PLN.
Testing Strategy
This test provides full coverage of all coding exons of the PLN 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 DCM or HCM, who have no variants reported in genes that are more frequently associated with DCM or HCM.
Patients with symptoms suggestive of DCM or HCM, who have no variants reported in genes that are more frequently associated with DCM or HCM.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| PLN | 172405 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Dilated Cardiomyopathy 1P | 609909 | |
| Familial Hypertrophic Cardiomyopathy 18 | 613874 |
Related Test
| Name |
|---|
| Dilated Cardiomyopathy via the LAMA4 Gene |
Citations
- Chiu, C., et.al. (2007). "Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy." J Mol Cell Cardiol 43(3): 337-43. PubMed ID: 17655857
- 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
- Grünig E. et al. 1998. Journal of the American College of Cardiology. 31: 186-94. PubMed ID: 9426039
- Haghighi, K., et.al. (2008). "A human phospholamban promoter polymorphism in dilated cardiomyopathy alters transcriptional regulation by glucocorticoids." Hum Mutat 29(5): 640-7. PubMed ID: 18241046
- Hershberger RE, Morales A. 2013. Dilated Cardiomyopathy Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301486
- Ikram H. et al. 1987. British heart journal. 57: 521-7. PubMed ID: 3620228
- Landstrom, A. P., et.al. (2011). "PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing." Am Heart J 161(1): 165-71. PubMed ID: 21167350
- Møller DV. et al. 2009. European journal of human genetics : EJHG. 17: 1241-9. PubMed ID: 19293840
- 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
- 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
- Schmitt, J. P., et.al. (2003). "Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban." Science 299(5611): 1410-3. PubMed ID: 12610310
- Tamburro P., Wilber D. 1992. American heart journal. 124: 1035-45. PubMed ID: 1529877
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
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ORDER OPTIONS
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2) Select Additional Test Options
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