Ventricular Septal Defects, Tetralogy of Fallot via the FOXH1 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 | |
|---|---|---|---|---|---|
| 9157 | FOXH1 | 81479 | 81479,81479 | $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
Heterotaxy syndrome or situs ambiguus results from a failure to properly establish left-right asymmetry during embryogenesis resulting in an abnormal arrangement of thoracic or abdominal visceral organs, including the heart, lungs, liver, spleen, intestines, and stomach. Affected patients frequently have significant morbidity and mortality due to a wide variety of cyanotic congenital heart defects. Common defects besides cardiac malformations include asplenia or polysplenia, left-sided liver, right-sided stomach, gastrointestinal malrotation, and altered lung lobation. Classic heterotaxy (cardiac malformations and visceral laterality defects) has an estimated prevalence of 1:10,000 live births (Lin et al. Genet Med 2:157-172, 2000).
Genetics
Heterotaxy is a heterogeneous genetic disorder. Variants in at least 7 genes (NODAL, ZIC3, CFC1, FOXH1, LEFTY2, GDF1, and ACVR2B) involved in NODAL signaling have been proposed to cause heterotaxy or congenital heart defects (CHDs). These proteins play an essential role in establishing left-right patterning during organogenesis, including the heart and great vessels (reviewed by Hamada et al. Nat Rev Genet 3:103-113, 2002). Defects in NODAL signaling factors are also found in 5-10% of patients with isolated CHDs without heterotaxy, including tetralogy of Fallot, double outlet right ventricle, transposition of the great arteries, and cardiac septal defects (Roessler et al. Am J Hum Genet 83:18-29, 2008; Mohapatra et al. Hum Mol Genet 18:861-871, 2009). FOXH1 (OMIM 603621) encodes a forkhead transcription factor that mediates NODAL signaling. Variants in FOXH1 exhibit autosomal dominant inheritance. A heterozygous frameshift variant was found in FOXH1 in a Chinese patient with a ventricular septal defect (Wang et al. In J Cardiol 145:83-85, 2010). One patient with transposition of the great arteries harbored heterozygous missense variants in FOXH1 and ZIC3 (De Luca et al. Heart 96:673-677, 2010). Seven unrelated individuals with complex CHDs including tetralogy of Fallot were found to harbor potentially disruptive sequence variants in FOXH1 (Roessler et al. Am J Hum Genet 83:18-29, 2008).
Clinical Sensitivity - Sequencing with CNV PGxome
Variants in the FOXH1 gene are estimated to cause <1% of all cases of heterotaxy and CHDs (Roessler et al. Am J Hum Genet 83:18-29, 2008; Wang et al. Int J Cardiol 145:83-85, 2010; De Luca et al. Heart 96:673- 677, 2010).
Testing Strategy
This test provides full coverage of all coding exons of the FOXH1 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
All patients with heterotaxic phenotypes are candidates for this test. Patients with isolated CHDs without visceral laterality defects are also candidates for this test (Wang et al. Int J Cardiol 145:83-85, 2009).
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| FOXH1 | 603621 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|
Citations
- De Luca et al. (2010). Familial transposition of the great arteries caused by multiple mutations in laterality genes. Heart 96(9):673-677. PubMed ID: 19933292
- De Luca et al. (2010). Familial transposition of the great arteries caused by multiple mutations in laterality genes. Heart 96(9):673-677. PubMed ID: 19933292
- Hamada, H., et.al. (2002). "Establishment of vertebrate left-right asymmetry." Nat Rev Genet 3(2): 103-13. PubMed ID: 11836504
- Lin AE, Ticho BS, Houde K, Westgate MN, Holmes LB. 2000. Heterotaxy: associated conditions and hospital-based prevalence in newborns. Genet. Med. 2: 157–172. PubMed ID: 11256661
- Mohapatra, B., et.al. (2009). "Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations." Hum Mol Genet 18(5): 861-71. PubMed ID: 19064609
- Roessler, E., et.al. (2008). "Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly." Am J Hum Genet 83(1): 18-29. PubMed ID: 18538293
- Roessler, E., et.al. (2008). "Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly." Am J Hum Genet 83(1): 18-29. PubMed ID: 18538293
- Wang et al. (2010). Forkhead box H1 (FOXH1) sequence variants in ventricular septal defect. Int J Cardiol 145(1):83-85. PubMed ID: 19525021
- Wang et al. (2010). Forkhead box H1 (FOXH1) sequence variants in ventricular septal defect. Int J Cardiol 145(1):83-85. PubMed ID: 19525021
- Wang et al. (2010). Forkhead box H1 (FOXH1) sequence variants in ventricular septal defect. Int J Cardiol 145(1):83-85. PubMed ID: 19525021
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
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.