X-linked Heterotaxy (HTX1) via the ZIC3 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8819 ZIC3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8819ZIC381479 81479 $890 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average


Genetic Counselors


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 and/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).


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). X-linked heterotaxy 1 (HTX1; OMIM 306955) is due to variants (missense, nonsense, frameshifts) in the zinc finger transcription factor ZIC3. Although males are most commonly affected, there are reports in the literature of symptomatic heterozygous females (Gebbia et al. Nature 17:305- 308, 1997; Ware et al. Am J Hum Genet 74:93-105, 2004; Chhin et al. Hum Mutat 28:563-570, 2007). Patients with isolated CHDs without any evidence for heterotaxy have also been found to harbor variants in ZIC3 (Megarbane et al. Eur J Hum Genet 8:704-708, 2000). A 1.3 Mb deletion of Xq26.3 including the ZIC3 locus has been found to segregate in an Italian family with heterotaxy (Chung et al. Am J Hum Genet 155A:1123-1128, 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

Variants in the ZIC3 gene are estimated to cause >75% of familial X-linked cases of heterotaxy, ~1% of sporadic cases of heterotaxy, and ~1% of cases with isolated CHDs without laterality defects (Ware et al. Am J Hum Genet 74:93-105, 2004).

Testing Strategy

This test provides full coverage of all coding exons of the ZIC3 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

All patients with heterotaxic phenotypes are candidates for this test. Patients with isolated CHDs without visceral laterality defects are also candidates for this test.


Official Gene Symbol OMIM ID
ZIC3 300265
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Heterotaxy, Visceral, X-Linked XL 306955

Related Test

Comprehensive Cardiology Panel


  • Chhin, B., et.al. (2007). PubMed ID: 17295247
  • Chung, B., et.al. (2011). PubMed ID: 21465648
  • Gebbia, M., et.al. (1997). PubMed ID: 9354794
  • Hamada, H., et.al. (2002). 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
  • Megarbane, A., et.al. (2000). PubMed ID: 10980576
  • Roessler, E., et.al. (2008). PubMed ID: 18538293
  • Ware, S. M., et.al. (2004). PubMed ID: 14681828


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.

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

Specimen Types

Specimen Requirements and Shipping Details

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View Ordering Instructions

1) Select Test Type

2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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