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Fibrodysplasia Ossificans progressiva (FOP) via the ACVR1 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
8293 ACVR1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8293ACVR181479 81479,81479 $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.

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 backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition characterized by congenital malformed great toes and postnatal progressive ectopic formation in muscles, tendons, ligament and fascia. The ectopic bone formation can occur spontaneously or be induced by minimal trauma. The worldwide prevalence of this disease is 1 in 2 million individuals. Most patients will lose mobility in the majority of their body caused by heterotopic bone formation by their 30s. Other features of FOP include hypoplasia thumbs and conductive hearing loss (Kaplan et al. 2008; Shore and Kaplan 2010; Huning and Gillessen-Kaesbach 2014).

Genetics

Heterozygous activating pathogenic variants in the ACVR1 gene cause autosomal dominant FOP. ACVR1 protein (activin receptor type I protein) is a mediator of bone morphogenetic protein type I receptors, which play key functions during embryonic development and postnatal life. To date, only 16 ACVR1 pathogenic variants have been reported, all of them are missense variants except one small in-frame deletion (Human Gene Mutation Database) and all of them are located in the glycine/serine-rich domain and the protein kinase domain of the ACVR1 protein. The penetrance for an individual who carries a heterozygous ACVR1 variant is complete. The majority of these pathogenic variants occur de novo (Bravenboer et al. 2015; Lee et al. 2009). Approximately 97% of FOP patients have the c.617G>A, p.Arg206His variant (Shore et al. 2006; Kaplan et al. 2012; Huning and Gillessen-Kaesbach 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in ACVR1 were found in 100% of individuals with FOP. Sequencing analysis can detect 100% of reported pathogenic variants in the ACVR1 gene (Kaplan et al. 2012; Bravenboer et al. 2015).

To date, no gross deletions or duplications have been reported in the ACVR1 gene (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the ACVR1 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 symptoms consistent with FOP, and the family members of patients who have known ACVR1 pathogenic variants (Bravenboer et al. 2015).

Gene

Official Gene Symbol OMIM ID
ACVR1 102576
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Fibrodysplasia Ossificans Progressiva AD 135100

Citations

  • Bravenboer N, Micha D, Triffit JT, Bullock AN, Ravazollo R, Bocciardi R, Rocco M di, Netelenbos JC, Ten Dijke P, Sánchez-Duffhues G, Kaplan FS, Shore EM, et al. 2015. Clinical Utility Gene Card for: Fibrodysplasia ossificans progressiva. Eur J Hum Genet. PubMed ID: 25604857
  • Hüning I, Gillessen-Kaesbach G. 2014. Fibrodysplasia Ossificans Progressiva: Clinical Course, Genetic Mutations and Genotype-Phenotype Correlation. Mol Syndromol 5: 201-211. PubMed ID: 25337067
  • Human Gene Mutation Database (Bio-base).
  • Kaplan FS, Chakkalakal SA, Shore EM. 2012. Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis. Dis Model Mech 5: 756-762. PubMed ID: 23115204
  • Kaplan FS, Merrer M Le, Glaser DL, Pignolo RJ, Goldsby RE, Kitterman JA, Groppe J, Shore EM. 2008. Fibrodysplasia ossificans progressiva. Best practice & research Clinical rheumatology 22: 191-205. PubMed ID: 18328989
  • Lee DY, Cho T-J, Lee HR, Park MS, Yoo WJ, Chung CY, Choi IH. 2009. ACVR1 Gene Mutation in Sporadic Korean Patients with Fibrodysplasia Ossificans Progressiva. J Korean Med Sci 24: 433-437. PubMed ID: 19543505
  • Shore EM, Kaplan FS. 2010. Inherited human diseases of heterotopic bone formation. Nat Rev Rheumatol 6: 518-527. PubMed ID: 20703219
  • Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho T-J, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, et al. 2006. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38: 525-527. PubMed ID: 16642017

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.

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