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Hereditary Hemochromatosis via the TFR2 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4069 TFR2 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4069TFR281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

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.


Genetic Counselors


  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

TFR2-related hereditary hemochromatosis (TFR2-HCC) is a disorder characterized by excess iron overload due to increased intestinal iron absorption. Symptom onset primarily occurs after the second decade of life with fatigue and arthralgia being initial signs of disease. TFR2-HCC, if untreated, can result in advanced disease including hepatomegaly, hepatic cirrhosis, hypogonadism, diabetes, arthritis, and cardiomyopathy. To date, less than 50 cases of TFR2-HCC have been reported with disease primarily occurring in patients of Japanese and Italian descent (Camaschella 2011). There are six types of hemochromatosis each due to a different genetic cause: type 1- HFE, type 2- HAMP or HJV/HFE2, type 3- TFR2, type 4- SLC40A1, type 5- FTH1, and type 6- FTL. Type 1 hemochromatosis is the most prevalent form of the disease and represents >90% of cases (Vujic 2014). Genetic testing can be helpful in differential diagnosis of HH from other liver function disorders and for determining the underlying cause of hemochromatosis (Zarrilli et al. 2013). Phlebotomy is standard treatment to reduce serum iron levels and prevent progressive liver damage.


Hemochromatosis is inherited in an autosomal recessive mode through pathogenic variants in the HFE, HAMP, HFE2/HJV, or TFR2 genes or an autosomal dominant pattern through pathogenic variants in the SLC40A1, FTH1, or FTL genes (Santos et al. 2012). The c.313C>T (p.Arg105*), c.515T>A (p.Met172Lys), c.750C>G (p.Tyr250*), c.88dupC (p.Arg30Profs*31), and c.1861_1872del (p.Ala621_Gln624del) variants account for nearly half of TFR2-HCC cases (Camaschella et al. 2000; Le Gac et al. 2004; Roetto et al. 2001; Camaschella 2011). Missense and nonsense pathogenic variants have been reported throughout the coding region in the TFR2 gene. Indels, splice site alterations have also been seen in only a few individuals. There is no clear genotype/phenotype correlation, and penetrance is variable (Camaschella 2011; Bardou-Jacquet et al. 2013). Co-occurrence of HFE and TFR2 pathogenic variants has been reported in patients with TFR2-HCC (Roetto et al. 2001; Pietrangelo et al. 2005). The TFR2 gene encodes the transferrin receptor 2 protein that is primarily expressed in hepatocytes. The transferrin receptor 2 protein regulates hepcidin levels, which are responsible for controlling intestinal iron absorption (Robb and Wesslin-Resnick 2004).

Clinical Sensitivity - Sequencing with CNV PG-Select

Analytical sensitivity should be high because all pathogenic variants reported to date are detectable by sequencing. Clinical sensitivity cannot be estimated because only a small number of patients have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the TFR2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for testing include individuals with liver histology indicated iron stores, serum transferrin iron saturation (>45%) and elevated serum ferritin concentration (>200 μg/L in females and >300 μg/L in males). Secondary findings including liver cirrhosis, diabetes mellitus and arthropathy may also be indicative of TFR2-HCC (Camaschella 2011). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TFR2.


Official Gene Symbol OMIM ID
TFR2 604720
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Hemochromatosis Type 3 AR 604250

Related Test

Hereditary Hemochromatosis Panel


  • Bardou-Jacquet E. et al. 2014. Clinics and Research in Hepatology and Gastroenterology. 38: 143-54. PubMed ID: 24321703
  • Camaschella C. et al. 2000. Nature Genetics. 25: 14-5. PubMed ID: 10802645
  • Camaschella C. et al. 2011. TFR2-Related Hereditary Hemochromatosis. 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: 20301523
  • Le Gac G. et al. 2004. Human Molecular Genetics. 13: 1913-8. PubMed ID: 15254010
  • Pietrangelo A. et al. 2005. Gastroenterology. 128: 470-9. PubMed ID: 15685557
  • Robb A., Wessling-Resnick M. 2004. Blood. 104: 4294-9. PubMed ID: 15319276
  • Roetto A. et al. 2001. Blood. 97: 2555-60. PubMed ID: 11313241
  • Santos P.C. et al. 2012. International Journal of Molecular Sciences. 13: 1497-511. PubMed ID: 22408404
  • Vujic M. 2014. Frontiers in Pharmacology. 5: 42. PubMed ID: 24653703
  • Zarrilli F. et al. 2013. Biomed Research International. 2013: 1-7. PubMed ID: 24222913


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

Specimen Types

Specimen Requirements and Shipping Details

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View Ordering Instructions

1) Select Test Method (Platform)

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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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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