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von Willebrand Disease Types 1, 2, and 3 via the VWF 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
11801 VWF 81408 81408,81479 $1100 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11801VWF81408 81408,81479 $1100 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

  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

von Willebrand Disease (VWD) is one of the most common inherited bleeding disorders worldwide with a prevalence of ~1% of the normal population (Werner et al. 1993) . VWD is caused by defective or deficient von Willebrand Factor (VWF) (Ginsburg et al. 1985). VWF is a large, multimeric glycoprotein that is released into the blood from endothelial cells and platelets and plays a key role in hemostasis through binding with the platelet GP1Bα receptors (See Bernard Soulier Syndrome) and by transporting factor VIII to sites of vascular damage (Goodeve 2010). Symptoms of VWD are present from birth, but may become more severe with hemostatic challenge and with increasing age. There are three main types of VWD and several subtypes (Sadler et al. 2006):

Type 1 VWD--accounts for ~70% of cases. Mutations are identified in ~65% of cases. Autosomal dominant inheritance with mild mucocutaneous bleeding and quantitative deficiency of VWF.
Type 2 VWD--accounts for ~25% of cases. Characterized by qualitatively defective VWF and is divided into four subgroups based upon the defective function of VWF:
Type 2A-- mainly autosomal dominant, some recessive inheritance with mild to moderate mucocutaneous bleeding due to reduced platelet interactions.
Type 2B-- autosomal dominant inheritance with mild to moderate mucocutaneous bleeding and potential thrombocytopenia; type 2B is associated with enhanced platelet interactions.
Type 2M-- autosomal dominant inheritance with mild to moderate mucocutaneous bleeding due to reduced platelet interactions.
Type 2N-- autosomal recessive inheritance, mimics mild hemophilia A and is characterized by excessive bleeding with hemostatic challenge (e.g. surgery); type 2N is associated with impaired binding of VWF to factor VIII.
Type 3 VWD-- accounts for ~5% of cases. Mutations are identified in up to 90% of cases. Autosomal recessive inheritance with severe mucocutaneous and musculoskeletal bleeding due to nearly complete quantitative deficiency of VWF.

See also Goodeve and James 2011. 

Genetics

VWD is inherited in either an autosomal dominant or recessive manner (see Clinical Features). Causative mutations are primarily missense or nonsense mutations located throughout the VWF gene, but found in particularly high numbers in select exons including exons 18-21 and 25-28. Approximately 50% of mutations in type 1 VWD are found between exons 18 and 28, and most mutations found with types 2A, 2B, and 2M are located in exon 28. Type 2N is associated with a high frequency of mutations in exons 18-20, and in type 3 VWD, mutations are abundant throughout the VWF gene but are commonly found in exon 28 (Goodeve 2010). We note that mutations in GP1BA result in a phenotype similar to VWD type 2B called platelet-type VWD.

Clinical Sensitivity - Sequencing with CNV PGxome

See Clinical Features for discussion of clinical sensitivity by type.

Large multi-exon and whole gene deletions make up approximately 5% of reported causative variants for the VWF gene (Yadegari et al. 2011; Goodeve 2010).

Testing Strategy

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

All patients with bleeding disorders and assays of hemostasis factors that suggest VWD (i.e. VWF:RCo, VWF:Ag, FVIII:C, etc.). Most patients have a positive family history. Patients with easy bruising, prolonged nosebleeds or bleeding following surgery or dental procedures, and patients with menorrhagia. In cases where DNA from an affected child is unavailable, we will sequence the gene in parents or other family members. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in VWF.

Gene

Official Gene Symbol OMIM ID
VWF 613160
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Ginsburg D, Handin RI, Bonthron DT, Donlon TA, Bruns GA, Latt SA, Orkin SH. 1985. Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization. Science 228: 1401–1406. PubMed ID: 3874428
  • Goodeve A, James P. 2011. von Willebrand Disease. 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: 20301765
  • Goodeve AC. 2010. The genetic basis of von Willebrand disease. Blood Reviews 24: 123–134. PubMed ID: 20409624
  • Sadler JE, Budde U, Eikenboom JCJ, Favaloro EJ, Hill FGH, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM. 2006. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. Journal of thrombosis and haemostasis 4: 2103–2114. PubMed ID: 16889557
  • Werner EJ, Broxson EH, Tucker EL, Giroux DS, Shults J, Abshire TC. 1993. Prevalence of von Willebrand disease in children: a multiethnic study. The Journal of pediatrics 123: 893–898. PubMed ID: 8229521
  • Yadegari H, Driesen J, Hass M, Budde U, Pavlova A, Oldenburg J. 2011. Large deletions identified in patients with von Willebrand disease using multiple ligation-dependent probe amplification: Letters to the Editor. Journal of Thrombosis and Haemostasis 9: 1083–1086. PubMed ID: 21410641

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.
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