PGmaxTM - Comprehensive Congenital Heart Disease Panel
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Panel CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 13008 | Genes x (509) | 81479 | 81161(x1), 81162(x1), 81307(x1), 81403(x3), 81404(x12), 81405(x30), 81406(x32), 81407(x10), 81408(x7), 81479(x918) | $1790 | Order Options and Pricing |
Pricing Comments
We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.
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).
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
Congenital heart disease (CHDs) encompasses a wide range of syndromic and non-syndromic conditions that feature structural abnormalities of the heart that arise during development. Non-syndromic congenital heart disease is one of the most common birth defects and occurs in 1-3% of live births (Hoffman and Kaplan. 2002. PubMed ID: 12084585; van der Linde et al. 2011. PubMed ID: 22078432). In syndromic disorders, CHDs are a significant source of morbidity and mortality. Structural defects can include (but are not limited to): conotruncal abnormalities (tetralogy of Fallot, double-outlet right ventricle (DORV), truncus arteriosus, transposition of the great arteries (TGA)), left ventricular outflow tract obstruction (coarctation of the aorta, aortic valve stenosis, bicuspid aortic valve, hypoplastic left heart), septal defects, cardiomyopathies, laterality defects (heterotaxy), aortopathies, and arrhythmia. CHDs most commonly present as isolated structural defects of the heart; however, they can also present as part of a syndrome. Syndromes that frequently present with CHDs include (but are not limited to): Alagille, RASopathy/Noonan spectrum, CHARGE, Holt-Oram, Kabuki, Coffin-Siris, Cornelia de Lange, Rubinstein-Taybi, and Adams-Oliver.
Improved surgical and medical interventions has resulted in increasing prevalence of CHDs in adults. Determining the genetic etiology of CHDs allows for the identification of potential unanticipated extracardiac involvement, assess recurrence risk in future pregnancies, and can provide a more accurate prognosis.
Genetics
The causes of congenital heart disease are many and varied, but some of the most common pathways include transcription factors important for heart development (NKX2-5, GATA4-6, HAND1, TBX1), genes involved in the RAS pathway resulting in RASopathy/Noonan syndrome phenotypes (PTPN11, SOS1, etc.), Notch signaling (JAG1, NOTCH1/2), and cilia function (Primary ciliary dyskinesia, Heterotaxy, Bardet-Biedl Syndrome, Joubert Syndrome).
CHDs are genetically heterogeneous and can be inherited in an autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL) manners. A wide range of genetic abnormalities, including aneuploidy (Down syndrome, Turner syndrome), chromosomal rearrangements, copy number variation (22q11.2 deletion syndrome, Williams-Beuren syndrome, Jacobsen syndrome, etc.), single nucleotide variants (SNVs), and insertions/deletions have been associated with CHDs.
Pathogenic copy number variants (CNVs) (karyotype and CMA) can explain 25-33% (Turan et al. 2018. PubMed ID: 29306563), while monogenic causes account for 6-30% of CHD cases (Blue et al. 2014. PubMed ID: 25500235; Jin et al. 2017. PubMed ID: 28991257; Hauser et al. 2018. PubMed ID: 29368431; Alankarage et al. 2019. PubMed ID: 30293987). De novo variants have been found to be enriched as well and potentially accounting for ~8% of cases of isolated CHD; however, not all of these genes have been definitively linked to CHD (Jin et al. 2017. PubMed ID: 28991257). While environmental factors cause ~2% of cases (Kuciene and Dulskiene. 2008. PubMed ID: 19124958), it is presumed that a large portion of the remaining unexplained cases are oligogenic or a combination of environmental and genetic factors.
See individual gene summaries for information on molecular biology of gene products and spectra of pathogenic variants.
| Syndrome | Gene(s) (some genes are listed more than once) |
| Nonsyndromic Heart Disease | ACTC1, ACVR1, CITED2, CRELD1, DCHS1, ELN, FLT4, GATA4, GATA5, GATA6, GJA1, HAND1, HAND2, JAG1, MCTP2, MED13L, MYH11, MYH6, MYH7, NKX2-5, NKX2-6, NOTCH1, NR2F2, PDGFRA, PRDM6, SMAD6, TAB2, TBX20, TLL1, ZFPM2 |
| Alagille Syndrome | JAG1, NOTCH2 |
| Cardiofaciocutaneous Syndrome | BRAF, KRAS, MAP2K1, MAP2K2 |
| Cantu Syndrome | ABCC9 |
| Char Syndrome | TFAP2B |
| CHARGE Syndrome | CHD7 |
| Costello Syndrome | HRAS |
| 22q11.2 Deletion Syndrome/DiGeorge Syndrome | TBX1 |
| Ellis-van Creveld Syndrome | EVC, EVC2 |
| Holt-Oram Syndrome | TBX5 |
| Kabuki Syndrome | KDM6A, KMT2D |
| Noonan Syndrome | BRAF, CBL, KAT6B, KRAS, LZTR1, MRAS, NF1, NRAS, PPP1CB, PTPN11, RAF1, RASA2, RIT1, RRAS, RRAS2, RRAS2, SHOC2, SOS1, SOS2 |
| Williams-Beuren Syndrome | ELN |
| Carpenter Syndrome | RAB23 |
| Coffin-Siris Syndrome | ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCB1, SMARCE1 |
| Cornelia de Lange Syndrome | HDAC8, NIPBL, SMC1A, SMC3 |
| Mowat-Wilson Syndrome | ZEB2 |
| Rubinstein-Taybi Syndrome | CREBBP, EP300 |
| Smith-Lemli-Opitz Syndrome | DHCR7 |
| Adams-Oliver Syndrome | ARHGAP31, DLL4, DOCK6, EOGT, NOTCH1, RBPJ |
| Baller-Gerold Syndrome | RECQL4 |
| Beckwith-Wiedemann Syndrome | CDKN1C |
| Coffin-Lowry Syndrome | RPS6KA3 |
| Duane-radial ray Syndrome | SALL4 |
| Nance-Horan Syndrome | NHS |
| Peter’s Plus Syndrome | B3GLCT |
| Roberts Syndrome | ESCO2 |
| Robinow Syndrome | ROR2, WNT5A |
| Saethre-Chotzen Syndrome | TWIST1 |
| Short rib polydactyly type | DYNC2H1 |
| Simpson-Golabi-Behmel Syndrome | GPC3 |
| Sotos Syndrome | NSD1 |
| Townes-Brocks Syndrome | SALL1 |
| Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder | CDK13 |
| Microphthalmia, syndromic | BCOR, STRA6 |
| Axenfeld-Rieger Syndrome | FOXC1, PITX2 |
| Baraitser-Winter Syndrome | ACTB, ACTG1 |
| Congenital heart defects and skeletal malformations | ABL1 |
| Weill-Marchesani Syndrome | ADAMTS10 |
| CHOPS Syndrome | AFF4 |
| Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis | AMMECR1 |
| Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects | B3GAT3 |
| Pulmonary hypertension | BMPR2 |
| Sifrim-Hitz-Weiss Syndrome | CHD4 |
| Mandibulofacial dysostosis, Guion-Almeida type | EFTUD2 |
| Kleefstra Syndrome | EHMT1 |
| Pulmonary venoocclusive disease | EIF2AK4 |
| Hereditary hemorrhagic telangiectasia | ENG |
| Cardiac valvular dysplasia | FLNA |
| Alveolar capillary dysplasia with misalignment of pulmonary veins | FOXF1 |
| Au-Kline Syndrome | HNRNPK |
| Athabaskan brainstem dysgenesis | HOXA1 |
| Cleft palate, cardiac defects, and mental retardation | MEIS2 |
| Feingold Syndrome | MYCN |
| Cardiac-urogenital syndrome | MYRF |
| Intellectual disability | NONO |
| Congenital heart defects and ectodermal dysplasia | PRKD1 |
| Verheij Syndrome | PUF60 |
| Smith-Magenis Syndrome | RAI1 |
| TARP Syndrome | RBM10 |
| Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart | RERE |
| Mullegama-Klein-Martinez Syndrome | STAG2 |
| Catel-Manzke Syndrome | TGDS |
| Intellectual developmental disorder with cardiac defects and dysmorphic facies | TMEM94 |
| Heterotaxy | ACVR2B, ANKS6, CFAP53, FOXH1, GDF1, LEFTY2, MMP21, NKX2-5, NODAL, PKD1L1, ZIC3 |
| Primary ciliary dyskinesia | CCDC65, CCNO, DNAH1, DNAH6, DNAH8, DNAJB13, DRC1, MCIDAS, OFD1, RPGR, RSPH1, RSPH3, RSPH4A, RSPH9 |
| Primary ciliary dyskinesia/Heterotaxy | AK7, ODAD2/ARMC4, CCDC103, CDIN1/CCDC114, ODAD3/CCDC151, CCDC39, CCDC40, CFAP298, DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAH11, DNAH5, DNAI1, DNAI2, DNAL1, GAS8, INVS, LRRC6, NME8, DNAAF6/PIH1D3, SPAG1, ODAD4/TTC25, ZMYND10 |
| Polycystic kidney disease | GANAB, PKD1, PKD2, PKHD1 |
| Nephronophthisis | ANKS6, CEP164, CEP290, CEP83, DCDC2, GLIS2, IFT172, INVS, IQCB1, NEK8, NPHP1, NPHP3, NPHP4, RPGRIP1L, SDCCAG8, TMEM67, TTC21B, WDR19, ZNF423 |
| Meckel-Gruber Syndrome | MKS1, B9D1, B9D2, CC2D2A, CEP290, KIF14, NPHP3, RPGRIP1L, TCTN2, TMEM107, TMEM216, TMEM231, TMEM67 |
| Joubert Syndrome | AHI1, ARL13B, ARL13B, B9D1, B9D2, C2CD3, CC2D2A, CEP104, CEP120, CEP290, CEP41, CEP41, CPLANE1, CSPP1, IFT172, INPP5E, KATNIP/KIAA0556, KIAA0586, KIAA0753, KIF7, MKS1, NPHP1, OFD1, PDE6B, PDE6D, PIBF1, POC1B, RPGRIP1L, TCTN1, TCTN2, TCTN3, TMEM107, TMEM138, TMEM216, TMEM231, TMEM237, TMEM67, TTC21B, ZNF423 |
| Bardet-Biedl Syndrome | ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CEP290, IFT172, IFT27, IFT27, LZTFL1, MKKS, MKS1, SDCCAG8, TRIM32, TTC8, WDPCP |
| Oral-facial-digital Syndrome | C2CD3, CPLANE1, DDX59, IFT57, INTU, KIAA0753, OFD1, SCLT1, TCTN3, TMEM107, TMEM138, TMEM216, TMEM231, TMEM231, WDPCP |
| Alström Syndrome | ALMS1 |
| McKusick-Kaufman Syndrome | MKKS |
| Ellis van Creveld Syndrome | EVC, EVC2 |
| Short rib thoracic dysplasia | CEP120, DYNC2H1, DYNC2LI1, IFT140, IFT172, IFT52, IFT80, KIAA0586, NEK1, DYNLT2B/TCTEX1D2, TTC21B, WDR19, DYNC2I2/WDR34, WDR35, DYNC2I1/WDR60 |
| Cranioectodermal dysplasia | IFT122, IFT43, WDR19, WDR35 |
| Carpenter Syndrome | RAB23, MEGF8 |
| Marfan Syndrome | FBN1 |
| Familial Thoracic Aortic Aneurysm | ACTA2, MYH11, TGFBR2 |
| Loeys-Dietz Syndrome | SMAD3, TGFBR1, TGFBR2 |
| Ehlers-Danlos Syndrome | COL3A1, COL5A1, COL5A2 |
| Congenital Contractural Arachnodactyly | FBN2 |
| Long QT Syndrome | AKAP9, ANK2, CACNA1C, CALM1, CALM2, CALM3, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNQ1, SCN4B, SCN5A, SNTA1, TRDN |
| Brugada Syndrome | ABCC9, CACNA1C, CACNA2D1, CACNB2, GPD1L, HCN4, KCND3, KCNE3, KCNE5, KCNH2, KCNJ8, PKP2, RANGRF, SCN10A, SCN1B, SCN2B, SCN3B, SCN5A, SLMAP, TRPM4 |
| Short QT Syndrome | CACNA1C, CACNA2D1, CACNB2, KCNH2, KCNJ2, KCNQ1 |
| Catecholaminergic Polymorphic Ventricular Tachycardia | ANK2, CALM1, CALM2, CALM3, CASQ2, KCNJ2, KCNQ1, RYR2, SCN5A, TRDN |
| Atrial fibrillation | GJA5 |
| Cardiomyopathy (Dilated, Hypertrophic, Left ventricular noncompaction, Arrhythmogenic right ventricular cardiomyopathy) | ABCC9, ACTC1, ACTN2, ALMS1, ANKRD1, BAG3, CAV3, CDH2, CRYAB, CSRP3, CTNNA3, DES, DMD, DOLK, DSC2, DSG2, DSP, DTNA, EMD, EYA4, FHL1, FHL2, FKTN, FLNC, GAA, GATAD1, GLA, ILK, JPH2, JUP, KRAS, LAMA4, LAMP2, LDB3, LMNA, MIB1, MYBPC3, MYH6, MYH7, MYL2, MYL3, MYLK2, MYOZ2, MYPN, NEBL, NEXN, NKX2-5, PDLIM3, PKP2, PLN, PPCS, PRDM16, PRKAG2, PRKAR1A, PTPN11, RAF1, RBM20, RYR2, SCN5A, SCO2, SGCD, TAFAZZIN, TCAP, TGFB3, TMEM43, TMPO, TNNC1, TNNI3, TNNT2, TPM1, TTN, TTR, TXNRD2, VCL |
| Diamond-Blackfan Anemia | GATA1, RPL5, RPS7, RPS10, RPL11, RPL15, RPS17, RPS19, RPS24, RPS26, RPL26, RPL35A |
| Fanconi Anemia | BRCA1, BRCA2, BRIP1, ERCC4, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MAD2L2, PALB2, RAD51, RAD51C, RFWD3, SLX4, UBE2T, XRCC2 |
For more information Pierpont et al. recently reviewed the genetics of congenital heart disease (Pierpont et al. 2018. PubMed ID: 30571578).
Clinical Sensitivity - Sequencing with CNV PGxome
The exact sensitivity of this panel is not known and will vary based on the disorder present in the patient. However, one study of copy number variation (CNV) in CHD using conventional karyotyping and chromosomal microarray (CMA) has found pathogenic CNVs in 14% of cases by karyotype and 24% by CMA (Turan et al. 2018. PubMed ID: 29306563). Studies using whole exome or genome sequencing have found pathogenic variants in 6-30% of cases (Blue et al. 2014. PubMed ID: 25500235; Jin et al. 2017. PubMed ID: 28991257; Hauser et al. 2018. PubMed ID: 29368431; Alankarage et al. 2019. PubMed ID: 30293987).
For CNV and genome/exome sequencing studies the yield in syndromic cases was significantly higher compared to isolated CHD. Pathogenic CNVs were found in 26% and 6% of cases in syndromic vs isolated CHDs, respectively (Turan et al. 2018. PubMed ID: 29306563). This same pattern was found in one genome sequencing study as pathogenic variants were found in 30% and 16% of cases in syndromic vs isolated CHDs, respectively (Alankarage et al. 2019. PubMed ID: 30293987).
Testing Strategy
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This panel typically provides 97.9% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing. Some exons cannot be efficiently captured, and some genes cannot be accurately sequenced because of the presence of multiple copies in the genome (of special note NOTCH2 exons 1-4 cannot be captured). Therefore, a small fraction of sequence variants relevant to the patient's health may not be detected.
Exome wide CNV is included in this test to allow for detection of microdeletion/duplication syndromes associated with CHD.
The report will not include all the observed rare variants due to the large number of genes included in the comprehensive CHD panel. Pathogenic, Likely Pathogenic, and Variants of Uncertain Significance considered to contribute to the proband's phenotype will be reported. CNVs that are found to encompass all or part of a gene(s) that is known or possibly associated with the patient’s phenotype will also be reported. A list of all rare variants included in this panel is available along with our interpretations upon request.
Reports will consist of two different sections:
- Variants in genes known to be associated with the provided phenotype
- Variants in genes possibly associated with the provided phenotype
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
All patients with isolated or syndromic congenital heart defects are candidates for testing.
All patients with isolated or syndromic congenital heart defects are candidates for testing.
Genes
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
Related Test
| Name |
|---|
| PGxome® |
Citations
- Alankarage et al. 2018. PubMed ID: 30293987
- Blue et al. 2014. PubMed ID: 25500235
- Hauser et al. 2018. PubMed ID: 29368431
- Hoffman and Kaplan. 2002. PubMed ID: 12084585
- Jin et al. 2017. PubMed ID: 28991257
- Kuciene and Dulskiene. 2008. PubMed ID: 19124958
- Pierpont et al. 2018. PubMed ID: 30571578
- Turan et al. 2018. PubMed ID: 29306563
- van der Linde et al. 2011. PubMed ID: 22078432
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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