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Knobloch Syndrome, Type I via the COL18A1 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
COL18A1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7995COL18A181479 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


  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Knobloch syndrome, type I (KNOI; OMIM 267750) is characterized by major features of ophthalmic abnormalities and occipital encephalocele. While there is variability in clinical presentation both within and between families (Menzel et al. Hum Mutat 23:77-84, 2004), patients are uniformly affected with severe ophthalmic disease leading to vision loss (Sertié et al. Hum Mol Genet 9:2051-2058, 2000). Specific findings include high myopia, vitreoretinal degeneration with retinal detachment, and macular abnormalities. Controversy exists regarding the classification of the cranial defect as a true encephalocele or, alternatively, as an occipital scalp defect. Seaver et al. (Am J Med Genet 46:203-208, 1993) suggested in some cases the abnormality found associated with Knobloch syndrome is a scalp defect, but its occurrence should nonetheless alert clinicians to the possibility of a significant underlying midline defect. Patients with Knobloch syndrome have been found to have normal to above normal intelligence (Seaver et al., 1993). Neuronal migration defects have been reported for this disorder in two families (Kliemann et al. Am J Med Genet 119A:15-19, 2003). Endostatin is a 20 kDa carboxy terminal proteolytic cleavage product of type XVIII collagen that has been shown to be a potent antiangiogenic and antitumor compound (O’Reilly et al. Cell 88:277-285, 1997). An endostatin polymorphism has been shown to be a risk factor for prostate cancer (Iughetti et al. Cancer Res 61:7375-7378, 2001).


Knobloch syndrome is an autosomal recessive disorder caused by variants in the COL18A1 gene (Sertié et al. Hum Mol Genet 9:2051-2058, 2000). Evidence has been presented for a second causative locus (Menzel et al. Hum Mutat 23:77-84, 2004; Suzuki et al. Am J Hum Genet 71:1320-1329, 2002), although a second gene has not yet been identified. Almost all COL18A1 variants reported are nonsense or splice site variants. One COL18A1 missense variant (p.Asp1437Asn) located within the endostatin region has been reported to be causative for Knobloch syndrome (Menzel et al. 2004). Three isoforms of the alpha chain of collagen type XVIII are coded by exons 1-43 of the COL18A1 gene (OMIM 120328) located on chromosome 21q22.3. Isoforms 2 and 3, but not 1, are expressed in the retina (Sertié et al. 2000; Suzuki et al. 2002).

Clinical Sensitivity - Sequencing with CNV PGxome

Test sensitivity should be high in patients with clinical features consistent with Knobloch syndrome. Suzuki et al. (Am J Hum Genet 71:1320-1329, 2002) found two causative alleles in five of eight patients.

Testing Strategy

This test provides full coverage of all coding exons of the COL18A1 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

Individuals with high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities, and occipital encephalocele or congenital occipital scalp defect. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in COL18A1.


Official Gene Symbol OMIM ID
COL18A1 120328
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Knobloch Syndrome 1 AR 267750


  • Iughetti, P., et.al. (2001). "A polymorphism in endostatin, an angiogenesis inhibitor, predisposes for the development of prostatic adenocarcinoma." Cancer Res 61(20): 7375-8. PubMed ID: 11606364
  • Kliemann, S. E., et.al. (2003). "Evidence of neuronal migration disorders in Knobloch syndrome: clinical and molecular analysis of two novel families." Am J Med Genet A 119A(1): 15-9. PubMed ID: 12707952
  • Menzel, O., et.al. (2004). "Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin." Hum Mutat 23(1): 77-84. PubMed ID: 14695535
  • O'Reilly, M. S., et.al. (1997). "Endostatin: an endogenous inhibitor of angiogenesis and tumor growth." Cell 88(2): 277-85. PubMed ID: 9008168
  • Seaver, L. H., et.al. (1993). "Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome." Am J Med Genet 46(2): 203-8. PubMed ID: 8484411
  • Sertie, A. L., et.al. (2000). "Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome)." Hum Mol Genet 9(13): 2051-8. PubMed ID: 10942434
  • Suzuki, O. T., et.al. (2002). "Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome." Am J Hum Genet 71(6): 1320-9. PubMed ID: 12415512


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