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Paget Disease of Bone, Autosomal Recessive Osteopetrosis, and Familial Expansile Osteolysis via the TNFRSF11A 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
TNFRSF11A 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9939TNFRSF11A81479 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.


Genetic Counselors


  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Paget disease of bone (PDB, OMIM#602080) is the second most common metabolic bone disorder that affects up to 2–3% of the population aged >40 years. This disorder is characterized by focal areas of increased and disorganized bone turnover, leading to bone pain, deformity, pathological fracture, neurological complications, and an increased risk of osteosarcoma (Laurin et al. Am J Hum Genet 70:1582-1588, 2002). Osteopetrosis, autosomal recessive 7 (OPTB7, OMIM#612301) is a severe osteoclast-poor form of autosomal recessive osteopetrosis associated with hypogammaglobulinemia (Guerrini et al. Am J Hum Genet 83:64-76, 2008). Familial expansile osteolysis (FEO, OMIM#174810) is a rare bone disorder characterized by focal areas of increased bone remodeling. FEO is related to PDB but occurs in younger patients, and the skeletal involvement is more severe. The osteolytic lesions, which usually develop in the long bones during early adulthood, show increased osteoblast and osteoclast activity (Hughes et al. Nature Genet 24:45-48, 2000).


Genetic heterogeneity is evident in all three of the disorders listed above. TNFRSF11A-related PDB and FEO are inherited in an autosomal dominant manner. TNFRSF11A-related OPTB7 shows an autosomal recessive pattern. TNFRSF11A encodes receptor activator of nuclear factor-kappa-B (RANK), which is a type I transmembrane protein and contains 4 extracellular cysteine-rich repeats. RANK is essential for osteoclast formation. The causal variants are known to impair cleavage of the RANK signal peptide (Hughes et al. 2000) and to cause abnormal localization of RANK within the cell. Among the few reported cases with TNFRSF11A variants, missense and nonsense changes are associated with the OPTB7 phenotype, while small insertions or duplications are related to the PEO or PDB phenotypes.

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect disease variants in most individuals with a clinical diagnosis of OPTB7 (Guerrini et al. Am J Hum Genet 83:64-76, 2008). Sensitivity for PDB and FEO is currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the TNFRSF11A 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

Candidates for this test are patients with features consistent with FEO or OPTB7, PDB patients who tested negative for SQSTM1 (major PBD-causing gene), and family members of patients who have a known TNFRSF11A variant. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TNFRSF11A.


Official Gene Symbol OMIM ID
TNFRSF11A 603499
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Juvenile Paget Disease via the TNFRSF11B Gene
Osteopetrosis via the CLCN7 Gene
Osteopetrosis via the OSTM1 Gene
Osteopetrosis via the SNX10 Gene
Osteopetrosis via the TCIRG1 Gene
Osteopetrosis via the TNFSF11 Gene
Paget Disease of Bone (PDB) Panel
Paget Disease of Bone via the SQSTM1 Gene


  • Guerrini, M. M., et.al. (2008). PubMed ID: 18606301
  • Hughes, A. E., et.al. (2000). PubMed ID: 10615125
  • Laurin, N., et.al. (2002). PubMed ID: 11992264


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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View Ordering Instructions

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2) Select Additional Test Options

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