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Osteogenesis Imperfecta via the COL1A1 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
COL1A1 81408 81408,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4635COL1A181408 81408,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

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

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder characterized by frequent bone fractures with or without minimal trauma. Clinical signs of OI can range from mild to severe. In addition to bone fractures, patients may have scoliosis, bowing of long bones, short stature, blue sclera, hearing loss, dentin defects, muscle weakness or joint laxity. The incidence is approximately 6-7/100,000 (van Dijk et al. 2012). ~90% of clinically diagnosed OI is caused by mutations in the COL1A1 and COL1A2 genes, while ~10% is caused by mutations in the CRTAP, FKB10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, IFITM5, BMP1, TMEM38B and other undefined genes (van Dijk et al. 2012; Valadares et al. 2014).


Mutations in the COL1A1 gene cause autosomal dominant OI types I, II, III and IV, as well as Ehlers-Danlos syndrome and Caffey disease (Steiner et al. 2013). Type I OI is characterized by fractures, blue sclerae and hearing loss, but with minimal bone deformity and dentin defects. Type II OI is perinatal lethal with bowed long bones, severe bone fractures and early death due to respiratory failure caused by small thorax and rib fractures. Type III OI is the severe non-lethal form, patients may show dysmorphic facial features, blue sclerae, dentin defects, scoliosis and extremely short status. Type IV OI has mild to moderate bone deformity, and normal to grey sclerae. Type I collagen, containing two proα1 (I) and one proα2 (II) chains coded by COL1A1 and COL1A2 genes, respectively, is the major structural protein in bone, tendon and ligament. To date, more than 600 COL1A1 pathogenic variants have been documented (Human Gene Mutation Database). No clear genotype-phenotype correlation have been established, but some studies suggested that frameshift, nonsense and splice site mutations in COL1A1 and COL1A2 are seen more in patients affected with mild OI type I that lead to haploinsufficiency, while glycine substitutions in the conserved triple helix domain of the Type I collagen protein are common pathogenic variants in patients affected with OI types II and III (Ben Amor et al. 2011; van Dijk et al. 2013). Almost all cases of type II and type III OI are caused by de novo mutations in COL1A1 or COL1A2. Gonadal mosaicism may explain 3%-5% of cases. The penetrance for an individual who carries a heterozygous COL1A1 and COL1A2 mutation is complete.

Clinical Sensitivity - Sequencing with CNV PG-Select

Mutations in COL1A1 and COL1A2 were found in 90% of individuals with OI types I, II, III, or IV (Steiner et al. 2013). A recent study reported that COL1A1 and COL1A2 mutations were identified in 56% (14/35) and 44% (11/35) of the OI cases, respectively (Stephen et al. 2014). Sequencing analysis can detect more than 95% of mutations in the COL1A1 and COL1A2 genes, while deletion and duplication studies can detect 1% -2% of COL1A1 and COL1A2 mutations (van Dijk et al. 2012, Steiner et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the COL1A1 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 autosomal dominant OI, and the family members of patients who have known COL1A1 mutations (van Dijk et al. 2012).


Official Gene Symbol OMIM ID
COL1A1 120150
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

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  • Ben Amor IM, Glorieux FH, Rauch F. 2011. Genotype-Phenotype Correlations in Autosomal Dominant Osteogenesis Imperfecta. Journal of Osteoporosis 2011: 19. PubMed ID: 21912751
  • Human Gene Mutation Database (Bio-base).
  • Steiner RD, Adsit J, Basel D. 2013. COL1A1/2-Related Osteogenesis Imperfecta. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301472
  • Stephen J, Shukla A, Dalal A, Girisha KM, Shah H, Gupta N, Kabra M, Dabadghao P, Phadke SR. 2014. Mutation spectrum of COL1A1 and COL1A2 genes in Indian patients with osteogenesis imperfecta. Am. J. Med. Genet. 164: 1482-1489. PubMed ID: 24668929
  • Valadares ER, Carneiro TB, Santos PM, Oliveira AC, Zabel B. 2014. What is new in genetics and osteogenesis imperfecta classification? Jornal de Pediatria 90:536-41. PubMed ID: 25046257
  • van Dijk FS, Byers PH, Dalgleish R, Malfait F, Maugeri A, Rohrbach M, Symoens S, Sistermans EA, Pals G. 2011. EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta. European Journal of Human Genetics 20: 1119. PubMed ID: 21829228


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

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