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Osteopetrosis via the TCIRG1 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
7841 TCIRG1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7841TCIRG181479 81479,81479 $640 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.

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.


Genetic Counselors


  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Osteopetrosis (also called Marble bone disease) is a disorder of increased bone density and bone mass caused by malfunction of bone resorption. Affected patients are at high risk of frequent bone fractures, delayed healing, hip osteoarthritis and osteomyelitis. Some patients may have vision loss, hearing loss, paralysis of facial muscles, and bone marrow abnormalities caused by abnormal dense bone structure. Other features include short stature, development delay, dental abnormalities, hepatosplenomegaly, intellectual disability, and epilepsy (Tolar et al. 2004; Del Fattore et al. 2008; Sobacchi et al. 2013). Osteopetrosis is currently known to be caused by mutations in the following genes: CLCN7, LRP5, TCIRG1, TNFSF11, CA2, OSTM1, PLEKHM1, SNX10 and TNFRSF11A.


Mutations in the TCIRG1 gene cause autosomal recessive osteopetrosis type I (also called malignant infantile psteopetrosis, or Albers-Schoenberg). The TCIRG1 protein coded by the TCIRG1 gene is an A3 subunit of vacuolar H(+)-ATPase, which regulates the pH value of intracellular compartments to maintain proper function of osteoclasts during bone resorption. To date, more than 100 unique pathogenic variants have been reported. They are: 20% missense, 16% nonsense, 30% splicing, 26% small deletion and insertion. Only 4 gross deletions have been reported (Pangrazio et al; 2009; Human Gene Mutation Database). A few population specific pathogenic variants have been reported. For example, the c.1213G>A, p.Gly405Arg variant was found in in 8 of 9 Costa Rican families, and the c.1331G>T, p. Arg444Leu variant was found in 5 of 9 Costa Rican families (Sobacchi et al. 2001). A founder splicing pathogenic variant c.117+4 was found in the Ashkenazi Jewish population (Anderson et al. 2014).

Clinical Sensitivity - Sequencing with CNV PG-Select

In one study, TCIRG1 pathogenic variants were identified in 50% of the 42 unrelated patients with malignant infantile osteopetrosis (Sobacchi et al. 2001).

Testing Strategy

This test provides full coverage of all coding exons of the TCIRG1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with symptoms consistent with osteopetrosis and the family members of patients who have known TCIRG1 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TCIRG1.


Official Gene Symbol OMIM ID
TCIRG1 604592
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Osteopetrosis Autosomal Recessive 1 AR 259700

Related Tests

Juvenile Paget Disease via the TNFRSF11B Gene
Osteopetrosis via the CLCN7 Gene
Osteopetrosis via the TNFSF11 Gene
Paget Disease of Bone (PDB) Panel
Paget Disease of Bone via the SQSTM1 Gene
Paget Disease of Bone, Autosomal Recessive Osteopetrosis, and Familial Expansile Osteolysis via the TNFRSF11A Gene


  • Anderson SL, Jalas C, Fedick A, Reid KF, Carpenter TO, Chirnomas D, Treff NR, Ekstein J, Rubin BY. 2014. A founder mutation in the TCIRG1 gene causes osteopetrosis in the Ashkenazi Jewish population: A founder mutation in the TCIRG1 gene causes osteopetrosis. Clinical Genetics n/a-n/a. PubMed ID: 24989235
  • Del Fattore A. et al. 2008. Bone. 42: 19-29. PubMed ID: 17936098
  • Human Gene Mutation Database (Bio-base).
  • Pangrazio A, Caldana ME, Sobacchi C, Panaroni C, Susani L, Mihci E, Cavaliere ML, Giliani S, Villa A, Frattini A. 2009. Characterization of a Novel Alu-Alu Recombination-Mediated Genomic Deletion in the TCIRG1 Gene in Five Osteopetrotic Patients. J Bone Miner Res 24: 162–167. PubMed ID: 18715141
  • Sobacchi C, Frattini A, Orchard P, Porras O, Tezcan I, Andolina M, Babul-Hirji R, Baric I, Canham N, Chitayat D, Dupuis-Girod S, Ellis I, Etzioni A, Fasth A, Fisher A, Gerritsen B, Gulino V, Horwitz E, Klamroth V, Lanino E, Mirolo M, Musio A, Matthijs G, Nonomaya S, Notarangelo LD, Ochs HD, Superti Furga A, Valiaho J, van Hove JL, Vihinen M, Vujic D, Vezzoni P, Villa A. 2001. The mutational spectrum of human malignant autosomal recessive osteopetrosis. Hum. Mol. Genet. 10: 1767-1773. PubMed ID: 11532986
  • Sobacchi C, Schulz A, Coxon FP, Villa A, Helfrich MH. 2013. Osteopetrosis: genetics, treatment and new insights into osteoclast function. Nature Reviews Endocrinology 9: 522-536. PubMed ID: 23877423
  • Tolar J. et al. 2004. New England Journal of Medicine. 351: 2839-49. PubMed ID: 15625335


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 (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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