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Pan Cardiomyopathy Sequencing Panel

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits
TEST METHODS

Sequencing

Test Code Test Copy GenesCPT Code Copy CPT Codes
5263 ABCC9 81479 Add to Order
ACTC1 81405
ACTN2 81479
ALMS1 81479
ANKRD1 81405
BAG3 81479
BRAF 81406
CALR3 81479
CAV3 81404
CAVIN4 81479
CRYAB 81479
CSRP3 81479
DES 81405
DMD 81408
DOLK 81479
DPP6 81479
DSC2 81406
DSG2 81406
DSP 81406
DTNA 81479
EMD 81405
EYA4 81479
FHL1 81404
FHL2 81479
FKRP 81404
FKTN 81405
GAA 81406
GATAD1 81479
GLA 81405
HCN4 81479
HRAS 81404
ILK 81479
JPH2 81479
JUP 81406
KRAS 81405
LAMA4 81479
LAMP2 81405
LDB3 81406
LMNA 81406
MAP2K1 81406
MAP2K2 81406
MIB1 81479
MYBPC3 81407
MYH6 81407
MYH7 81407
MYL2 81405
MYL3 81405
MYLK2 81479
MYO6 81479
MYOZ2 81479
MYPN 81479
NEXN 81479
NKX2-5 81479
NRAS 81479
PDLIM3 81479
PKP2 81406
PLN 81403
PRDM16 81479
PRKAG2 81406
PRKAR1A 81479
PTPN11 81406
RAF1 81406
RBM20 81479
RYR2 81408
SCN5A 81407
SCO2 81404
SGCD 81405
SGCG 81405
SOS1 81406
TAZ 81406
TCAP 81479
TGFB3 81479
TGFBR2 81405
TMEM43 81406
TMPO 81479
TNNC1 81405
TNNI3 81405
TNNT2 81406
TPM1 81405
TTN 81479
TTR 81404
VCL 81479
Full Panel Price* $1980.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
5263 Genes x (82) $1980.00 81403, 81404(x6), 81405(x16), 81406(x18), 81407(x4), 81408(x2), 81479(x35) Add to Order
Pricing Comment

If you would like to order a subset of these genes contact us to discuss pricing.

Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

The sensitivity of this panel varies based on the type of disease. This test is predicted to detect causative variants in ~60% of Hypertrophic Cardiomyopathy patients (Morita et al. 2008; Hershberger et al. 2009), up to 30% of adults with Left Ventricular Noncompaction (Ichida et al 2001; Vatta et al. 2003; Hermida-Prieto et al. 2004; Klaassen et al. 2008; Hoedemaekers et al. 2010), 30-40% of patients with familial Dilated Cardiomyopathy (Hershberger and Morales 2013), and ~73% of patients with autosomal dominant or sporadic Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (McNally et al. 2014; Bhuiyan et al. 2009).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 ABCC9$690.00 81479 Add to Order
ACTC1$690.00 81479
ACTN2$690.00 81479
ALMS1$690.00 81479
BAG3$690.00 81479
BRAF$690.00 81479
CAV3$690.00 81479
CRYAB$690.00 81479
CSRP3$690.00 81479
DES$690.00 81479
DMD$690.00 81161
DSC2$690.00 81479
DSG2$690.00 81479
DSP$690.00 81479
DTNA$690.00 81479
EMD$690.00 81404
EYA4$690.00 81479
FKRP$690.00 81479
FKTN$690.00 81479
GAA$690.00 81479
GLA$690.00 81479
HCN4$690.00 81479
HRAS$690.00 81479
JUP$690.00 81479
KRAS$690.00 81479
LAMP2$690.00 81479
LDB3$690.00 81479
LMNA$690.00 81479
MAP2K1$690.00 81479
MAP2K2$690.00 81479
MYBPC3$690.00 81479
MYH6$690.00 81479
MYH7$690.00 81479
MYL2$690.00 81479
MYL3$690.00 81479
MYO6$690.00 81479
MYOZ2$690.00 81479
NKX2-5$690.00 81479
NRAS$690.00 81479
PKP2$690.00 81479
PLN$690.00 81479
PRKAG2$690.00 81479
PRKAR1A$690.00 81479
PTPN11$690.00 81479
RAF1$690.00 81479
RYR2$690.00 81479
SCN5A$690.00 81479
SGCD$690.00 81479
SGCG$690.00 81404
SOS1$690.00 81479
TAZ$690.00 81479
TCAP$690.00 81479
TGFB3$690.00 81479
TGFBR2$690.00 81479
TMEM43$690.00 81479
TMPO$690.00 81479
TNNC1$690.00 81479
TNNI3$690.00 81479
TNNT2$690.00 81479
TPM1$690.00 81479
TTN$690.00 81479
TTR$690.00 81479
VCL$690.00 81479
Full Panel Price* $1670.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
600 Genes x (63) $1670.00 81161, 81404(x2), 81479(x60) Add to Order
Pricing Comment

# of Genes Ordered

Total Price

1

$690

2

$730

3

$770

4-10

$840

11-30

$1,290

31-100

$1,670

Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Gross deletions or duplications not detectable by sequencing have been reported in CAV3, DES, DSP, NKX2-5, PKP2, RYR2 and SCN5A as individual cases (Human Gene Mutation Database).

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Clinical Features

Cardiomyopathies are disorders of the myocardium that manifest with various structural and functional changes of the heart. The expressivity of cardiomyopathy is highly variable and patients may present symptoms such as shortness of breath, fatigue, dizziness, fluttering, swelling in the ankles and legs, etc. (Maron et al. 2006; McNally et al. 2015). Clinical heterogeneity may be partially attributed to genetic heterogeneity of the cardiomyopathy disorders. The contribution of genetic factors varies by disorder subtypes and age of onset (Ackerman et al. 2011). Cardiomyopathies include a broad range of disorders, including Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy, and Left Ventricular Non-Compaction Cardiomyopathy. Pan cardiomyopathy panel testing could help with differential diagnosis and prognostic stratification for patients with cardiomyopathies (Charron et al. 2010).

Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) primarily affects the right ventricle. It is characterized by myocardial atrophy, fibrofatty replacement of the ventricular myocardium and inflammatory infiltrates (McNally et al. 2014).

Left Ventricular Noncompaction (LVNC) Cardiomyopathy is believed to be caused by an arrest in cardiac development during embryogenesis, resulting in a spongy, noncompacted appearance. The numerous trabeculations are most pronounced in the left ventricle (Oechslin et al. 2011; Hoedemaekers et al. 2010).

Dilated Cardiomyopathy (DCM) is a heterogeneous disease of the cardiac muscle characterized by dilatation of the left, right, or both ventricles, systolic dysfunction, and diminished myocardial contractility (Hershberger et al. 2013).

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 also occur. HCM is distinguished by extensive clinical variability between individuals, even within the same family (Cirino et al. 2014).

Genetics

Cardiomyopathy represents a group of genetically heterogeneous disorders with substantial genetic component. Genetic causes could contribute significantly in 60% of hypertrophic cardiomyopathy cases, and 30-50% of Dilated Cardiomyopathy cases (Teekakirikul et al. 2013). The inheritance mode of cardiomyopathy disorders include autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL). The majority of cardiac-related genes are associated with autosomal dominant disorders. The ALMS1, DOLK, FKRP, FKTN, GAA, GATAD1, LAMA2, SCO2, and SGCG are associated with autosomal recessive cardiac-related disorders. The DSC2, DSP, JUP, LMNA, SCN5A, TNNI3, and TTN genes are associated with autosomal dominant and recessive cardiac-related disorders. The FHL1, GLA, LAMP2, DMD, EMD, and TAZ genes are associated with X-linked recessive cardiac-related disorders, except for LAMP2, which is involved in X-linked dominant cardiac-related disorders (OMIM; Human Gene Mutation Database). See individual gene test descriptions for information on molecular biology of gene products.

Testing Strategy

For this Next Generation Sequencing (NGS) test, sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization kit, followed by massively parallel sequencing of the captured DNA fragments. Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads. All reported pathogenic, likely pathogenic, and variants of uncertain significance are confirmed by Sanger sequencing.

For Sanger sequencing, polymerase chain reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

This panel provides full coverage of all coding exons of the genes listed, plus ~20 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads for coding regions and 0-10 bases of flanking DNA, >10X NGS reads for 11-20 bases of flanking DNA, 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 and medical history suggestive of cardiomyopathy disorders.

Diseases

Name Inheritance OMIM ID
3-Methylglutaconic Aciduria Type 2 XL 302060
Alstrom Syndrome AR 203800
Amyloidogenic Transthyretin Amyloidosis AD 105210
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 1 AD 107970
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 10 AD 610193
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 11 AD,AR 610476
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 12 AD 611528
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 2 AD 600996
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 5 AD 604400
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 8 AD 607450
Arrhythmogenic Right Ventricular Cardiomyopathy, Type 9 AD 609040
Atrial Fibrillation, Familial, 10 AD 614022
Atrial Fibrillation, Familial, 12 AD 614050
Atrial Septal Defect 3 AD 614089
Atrial Septal Defect 5 AD 612794
Atrial Septal Defect With Atrioventricular Conduction Defects AD 108900
Brugada Syndrome 1 AD 601144
Cardioencephalomyopathy, Fatal Infantile, due to Cytochrome c Oxidase Deficiency 1 AR 604377
Cardiofaciocutaneous syndrome 2 AD 615278
Cardiofaciocutaneous syndrome 3 AD 615279
Cardiofaciocutaneous syndrome 4 AD 615280
Cardiomyopathy Dilated With Woolly Hair And Keratoderma AR 605676
Cardiomyopathy, Dilated, 1Hh AD 613881
Cardiomyopathy, dilated, 1II AD 615184
Cardiomyopathy, dilated, 1JJ AD 615235
Cardiomyopathy, Dilated, 1KK AD 615248
Cardiomyopathy, Dilated, 2B AR 614672
Cardiomyopathy, Dilated, 3B XL 302045
Cardiomyopathy, Familial Hypertrophic, 17 AD 613873
Cardiomyopathy, Familial Hypertrophic, 19 AD 613875
Carney Complex, Type 1 AD 160980
Catecholaminergic Polymorphic Ventricular Tachycardia, 1 AD 604772
Congenital Disorder Of Glycosylation Type 1M AR 610768
Costello Syndrome AD 218040
Danon Disease XL 300257
Deafness, Autosomal Dominant 22 AD 606346
Dilated Cardiomyopathy 1A AD 115200
Dilated Cardiomyopathy 1Aa AD 612158
Dilated Cardiomyopathy 1C AD 601493
Dilated Cardiomyopathy 1CC AD 613122
Dilated Cardiomyopathy 1DD AD 613172
Dilated Cardiomyopathy 1I AD 604765
Dilated Cardiomyopathy 1J AD 605362
Dilated Cardiomyopathy 1L AD 606685
Dilated Cardiomyopathy 1N AD 607487
Dilated Cardiomyopathy 1P AD 609909
Dilated Cardiomyopathy 1R AD 613424
Dilated Cardiomyopathy 1S AD 613426
Dilated Cardiomyopathy 1X AR 611615
Dilated Cardiomyopathy 1Y AD 611878
Dilated Cardiomyopathy 2A AD 611880
Emery-Dreifuss Muscular Dystrophy 1, X-Linked XL 310300
Emery-Dreifuss muscular dystrophy-6 XL 300696
Fabry's Disease XL 301500
Fallot Tetralogy AD 187500
Familial Hypertrophic Cardiomyopathy 1 AD 192600
Familial Hypertrophic Cardiomyopathy 10 AD 608758
Familial Hypertrophic Cardiomyopathy 12 AD 612124
Familial Hypertrophic Cardiomyopathy 13 AD 613243
Familial Hypertrophic Cardiomyopathy 14 AD 613251
Familial Hypertrophic Cardiomyopathy 15 AD 613255
Familial Hypertrophic Cardiomyopathy 16 AD 613838
Familial Hypertrophic Cardiomyopathy 18 AD 613874
Familial Hypertrophic Cardiomyopathy 2 AD 115195
Familial Hypertrophic Cardiomyopathy 4 AD 115197
Familial Hypertrophic Cardiomyopathy 6 AD 600858
Familial Hypertrophic Cardiomyopathy 7 AD 613690
Familial Hypertrophic Cardiomyopathy 8 AD 608751
Familial Hypertrophic Cardiomyopathy 9 AD 613765
Glycogen Storage Disease Type II AR 232300
Left Ventricular Noncompaction 1 AD 604169
Left ventricular noncompaction 10 AD 615396
Left Ventricular Noncompaction 7 AD 615092
Left Ventricular Noncompaction 8 AD 615373
Loeys-Dietz Syndrome 2 AD 610168
Long QT Syndrome 9 AD 611818
Muscular Dystrophy, Limb Girdle, Type 2C AR 253700
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 5 AR 607155
Myofibrillar Myopathy, BAG3-Related AD 612954
Myopathy, X-Linked, With Postural Muscle Atrophy XL 300696
Noonan Syndrome 1 AD 163950
Noonan Syndrome 4 AD 610733
Noonan Syndrome 5 AD 611553
Noonan Syndrome 6 AD 613224
Noonan Syndrome 7 AD 613706
Sick Sinus Syndrome 2, Autosomal Dominant AD 163800
Ventricular Fibrillation, Paroxysmal Familial, 2 AD 612956
Ventricular Septal Defect 3 AD 614432
Wolff-Parkinson-White Pattern AD 194200

Related Tests

Name
BRAF-Related Disorders via the BRAF Gene
FHL1-Myopathies via the FHL1 Gene
KRAS-Related Disorders via the KRAS Gene
PRKAG2-Related Disorders via the PRKAG2 Gene
PTPN11-Related Disorders via the PTPN11 Gene
RAF1-Related Disorders via the RAF1 Gene
Alstrom Syndrome via the ALMS1 Gene
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia and DSP-Related Disorders via the DSP Gene
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Sequencing Panel
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia via the DSC2 Gene
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia via the DSG2 Gene
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia via the PKP2 Gene
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia via the TGFB3 Gene
Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia via the TMEM43 Gene
Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Panel
Autosomal Dominant Limb Girdle Muscular Dystrophy (LGMD) Sequencing Panel
Autosomal Recessive Limb Girdle Muscular Dystrophy (LGMD) Sequencing Panel
Barth Syndrome via the TAZ Gene
Brugada Syndrome 1 via the SCN5A Gene
Brugada Syndrome Sequencing Panel
Cantu Syndrome via the ABCC9 Gene
Cardio-Facio-Cutaneous Syndrome via the MAP2K1 Gene
Cardio-Facio-Cutaneous Syndrome via the MAP2K2 Gene
Carney Complex (CNC) via the PRKAR1A Gene
Catecholaminergic Polymorphic Ventricular Tachycardia Sequencing Panel
Catecholaminergic Polymorphic Ventricular Tachycardia via the RYR2 Gene
Caveolinopathy via the CAV3 Gene
Centronuclear Myopathy Sequencing Panel
Charcot Marie Tooth - Axonal Neuropathy Sequencing Panel
Charcot Marie Tooth - Comprehensive Sequencing Panel
Ciliopathy Sequencing Panel
Comprehensive Cardiac Arrhythmia Sequencing Panel
Comprehensive Cardiology Sequencing Panel
Comprehensive Fetal and Neonatal Loss Panel
Comprehensive Inherited Retinal Dystrophies (includes RPGR ORF15) Sequencing Panel
Comprehensive Neuromuscular Sequencing Panel
Comprehensive Neuropathy Sequencing Panel
Congenital Cataracts Sequencing Panel
Congenital Fiber Type Disproportion Sequencing Panel
Congenital Hypothyroidism and Thyroid Hormone Resistance Sequencing Panel
Congenital Muscular Dystrophy Sequencing Panel
Congenital Myopathy Sequencing Panel
Core Myopathy Sequencing Panel
Costello Syndrome via the HRAS Gene
Danon Disease/Glycogen Storage Disease IIb via the LAMP2 Gene
Deafness, Autosomal Dominant 10 (DFNA10) via the EYA4 Gene
Deafness, Autosomal Dominant 22 (DFNA22) and Deafness, Autosomal Recessive 37 (DFNB37) via the MYO6 Gene
Dilated Cardiomyopathy and Limb-Girdle Muscular Dystrophy Type 2F via the SGCD Gene
Dilated Cardiomyopathy Sequencing Panel
Dilated Cardiomyopathy via the ANKRD1 Gene
Dilated Cardiomyopathy via the LAMA4 Gene
Dilated Cardiomyopathy via the RBM20 Gene
Dilated Cardiomyopathy via the NEXN Gene
Disorders of Fatty Acid Oxidation Sequencing Panel
Distal Hereditary Myopathy Sequencing Panel
Dystroglycan-Related Congenital Muscular Dystrophy Sequencing Panel
Dystroglycanopathy via the FKTN Gene
Dystrophinopathy via the DMD Gene
Dystrophinopathy via the DMD Gene
Emery-Dreifuss Muscular Dystrophy (EDMD1) via the EMD Gene
Epidermolysis Bullosa and Related Disorders Sequencing Panel
Fabry Disease via the GLA Gene
Familial Amyloidosis via the TTR Gene
Familial Atrial Fibrillation Syndrome Sequencing Panel
Familial Thoracic Aortic Aneurysm and Dissection (TAAD) Sequencing Panel
Fetal Concerns Sequencing Panel
Fukuyama Congenital Muscular Dystrophy via the FKTN Japanese Founder Mutation
Glycogen Storage Disease and Disorders of Glucose Metabolism Sequencing Panel
Glycogen Storage Disease Type II (Pompe Disease) via the GAA Gene
Glycogen Storage Disease Type II (Pompe Disease) via the GAA Gene, Exon 18 Deletion
Heterotaxy and Conotruncal Heart Defects via the GDF1 Gene
Heterotaxy, Situs Inversus and Kartagener's Syndrome Sequencing Panel
Hutchinson-Gilford Progeria Syndrome (HGPS) via the LMNA Gene
Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy via the ACTN2 Gene
Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy via the CSRP3 Gene
Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy via the MYH6 Gene
Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy via the PLN Gene
Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy via the TPM1 Gene
Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy via the VCL Gene
Hypertrophic Cardiomyopathy and other MYH7-Related Disorders via the MYH7 Gene
Hypertrophic Cardiomyopathy and Related Disorders via the ACTC1 Gene
Hypertrophic Cardiomyopathy and Related Disorders via the TNNI3 Gene
Hypertrophic Cardiomyopathy and Related Disorders via the TNNT2 Gene
Hypertrophic Cardiomyopathy Sequencing Panel
Hypertrophic Cardiomyopathy via the MYBPC3 Gene
Hypertrophic Cardiomyopathy via the MYL2 Gene
Hypertrophic Cardiomyopathy via the MYL3 Gene
Hypertrophic Cardiomyopathy via the TNNC1 Gene
Isolated Nonsyndromic Congenital Heart Defects via the NKX2-5 Gene
Isolated Nonsyndromic Congenital Heart Defects via the ZFPM2 (FOG2) Gene
Laminopathies via the LMNA Gene
Left Ventricular Noncompaction (LVNC) Sequencing Panel
Left Ventricular Noncompaction (LVNC) via the DTNA Gene
Limb Girdle Muscular Dystrophy Type 2I via the FKRP Gene
Limb Girdle Muscular Dystrophy, Type 2C (LGMD2C) via the SGCG Gene
Limb Girdle Muscular Dystrophy, Type 2J and Tibial Muscular Dystrophy via the TTN Gene (exons 307 - 312)
Limb-Girdle Muscular Dystrophy (LGMD) Sequencing Panel
Loeys-Dietz Syndrome Sequencing Panel
Loeys-Dietz Syndrome via the TGFBR2 Gene
Long QT Syndrome Sequencing Panel
Marfan Syndrome and Related Aortopathies Sequencing Panel
Metabolic Myopathies, Rhabdomyolysis and Exercise Intolerance Sequencing Panel
Mitochondrial Complex IV Deficiency Sequencing Panel (Nuclear Genes)
Mitochondrial Complex IV Deficiency via the SCO2 Gene
Myofibrillar Myopathy Sequencing Panel
Myofibrillar Myopathy via the CRYAB Gene
Myofibrillar Myopathy via the DES Gene
Myofibrillar Myopathy via the LDB3 (ZASP) Gene
Myofibrillar Myopathy, Childhood Onset via the BAG3 Gene
Naxos Disease and Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia via the JUP Gene
Nonsyndromic Hearing Loss and Deafness Sequencing Panel
Noonan Spectrum Disorders/Rasopathies Sequencing Panel
Noonan Syndrome via the NRAS Gene
Noonan Syndrome via the SOS1 Gene
Sick Sinus Syndrome and Brugada Syndrome via the HCN4 Gene
Sudden Cardiac Arrest Sequencing Panel
Telethoninopathy via the TCAP Gene
X-Linked Intellectual Disability Sequencing Panel

CONTACTS

Genetic Counselors
Geneticist
Citations
  • Ackerman M.J. et al. 2011. Europace. 13: 1077-109. PubMed ID: 21810866
  • Bhuiyan Z.A. et al. 2009. Circulation. Cardiovascular Genetics. 2: 418-27. PubMed ID: 20031616
  • Charron P. et al. 2010. European Heart Journal. 31: 2715-26. PubMed ID: 20823110
  • Cirino, A.L., Ho, C. 2014. Hypertrophic 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: 20301725
  • Hermida-Prieto M. et al. 2004. The American Journal of Cardiology. 94: 50-4. PubMed ID: 15219508
  • Hershberger R.E. et al. 2009. Circulation. Heart Failure. 2: 253-61. PubMed ID: 19808347
  • Hershberger R.E., 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
  • Hoedemaekers Y.M. et al. 2010. Circulation. Cardiovascular Genetics. 3: 232-9. PubMed ID: 20530761
  • Human Gene Mutation Database (Bio-base).
  • Ichida F. et al. 2001. Circulation. 103: 1256-63. PubMed ID: 11238270
  • Klaassen S. et al. 2008. Circulation. 117: 2893-901. PubMed ID: 18506004
  • Maron B.J. et al. 2006. Circulation. 113: 1807-16. PubMed ID: 16567565
  • McNally E. et al. 2014. Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301310
  • McNally E.M. et al. 2015. Cell Metabolism. 21: 174-82. PubMed ID: 25651172
  • Morita H. et al. 2008. The New England Journal of Medicine. 358: 1899-908. PubMed ID: 18403758
  • Oechslin E., Jenni R. 2011. European Heart Journal. 32: 1446-56. PubMed ID: 21285074
  • Online Mendelian Inheritance in Man: http://www.omim.org/
  • Teekakirikul P. et al. 2013. The Journal of Molecular Diagnostics. 15: 158-70. PubMed ID: 23274168
  • Vatta M. et al. 2003. Journal of the American College of Cardiology. 42: 2014-27. PubMed ID: 14662268
Order Kits
TEST METHODS

Exome Sequencing

Test Procedure

For the PGxome we use Next Generation Sequencing (NGS) technologies to cover the coding regions of targeted genes plus ~10 bases of non-coding DNA flanking each exon. As required, genomic DNA is extracted from patient specimens. Patient DNA corresponding to these regions is captured using Agilent Clinical Research Exome hybridization probes. Captured DNA is sequenced using Illumina's Reversible Dye Terminator (RDT) platform NextSeq 500 using 150 by 100 bp paired end reads (Illumina, San Diego, CA, USA). The following quality control metrics are generally achieved: >97% of target bases are covered at >20x, and mean coverage of target bases >120x. Data analysis and interpretation is performed by the internally developed software Titanium-Exome. In brief, the output data from the NextSeq 500 is converted to fastqs by Illumina Bcl2Fastq 1.8.4, and mapped by BWA. Variant calls are made by the GATK Haplotype caller and annotated using in house software and SnpEff. Variants are filtered and annotated using VarSeq (www.goldenhelix.com). Common benign, likely benign, and low quality variants are filtered from analysis. All reported pathogenic, likely pathogenic, and variants of uncertain significance are confirmed by Sanger sequencing.

For Sanger sequencing, polymerase chain reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Analytical Validity
Analytical Limitations

Interpretation of the test results is limited by the information that is currently available. Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

When sequencing does not reveal any heterozygous differences from the reference sequence, we cannot be certain that we were able to detect both patient alleles. Occasionally, a patient may carry an allele which does not capture or amplify, due to a large deletion or insertion. In these cases, the report will contain no information about the second allele. Our Sanger and NGS tests (including PGxome) are generally not capable of detecting Copy Number Variants (CNVs).

For technical reasons, the PGxome test is not 100% sensitive. Some exons cannot be efficiently captured, and some genes cannot be accurately sequenced because of the presence of multiple copies in the genome. Therefore, a small fraction of sequence variants relevant to the patient's health will not be detected.

We sequence coding exons for most given transcripts, plus ~10 bp of flanking non-coding DNA for each exon. Unless specifically indicated, test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions, uncharacterized alternative exons, chromosomal rearrangements, repeat expansions, epigenetic effects, and mitochondrial genome variants.

In most cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants due to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient's nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during amplification.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes if taken from whole blood). Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics. However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.

A negative finding does not rule out a genetic diagnosis.

Genetic counseling to help to explain test results to the patients and to discuss reproductive options is recommended.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options


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.
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.

SPECIMEN TYPES
WHOLE BLOOD

(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.

DNA

(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.

CELL CULTURE

(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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