Test Catalog

Test Id : VWFNG

von Willebrand Disease, VWF Gene, Next-Generation Sequencing, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Genetic confirmation of hereditary von Willebrand disease with the identification of alterations in the VWF gene known or suspected to cause the condition

 

Testing for close family members of an individual with a von Willebrand disease diagnosis

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test detects pathogenic alterations within the VWF gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of von Willebrand disease (VWD), a bleeding disorder of variable severity.

 

The gene target for this test includes the following:

Gene name (transcript): VWF (GRCh37 (hg19) NM_000552)

Chromosomal location: 12p13.31

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
CULAF Amniotic Fluid Culture/Genetic Test Yes No
CULFB Fibroblast Culture for Genetic Test Yes No
MATCC Maternal Cell Contamination, B Yes No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

A clinical and laboratory testing algorithm for von Willebrand disease (VWD) has been developed by the National Heart, Lung, and Blood Institute of the National Institutes of Health that is freely available at https://www.nhlbi.nih.gov/health-pro/guidelines/current/von-willebrand-guidelines.

 

The laboratory workup for VWD is complex and requires initial coagulation screening (including a CBC, platelet count, partial thromboplastin time (PTT), prothrombin time (PT), and fibrinogen or thrombin time) should be performed prior to any consideration of genetic testing. Genetic testing should not be performed until a definitive diagnosis of VWD has been made.

 

Prenatal genetic testing is not performed without the prior identification of familial VWF alterations.

 

For any cord blood or prenatal specimen that is received, maternal cell contamination studies will be added. A maternal whole blood sample is required to perform this test.

 

If amniotic fluid is received, amniotic fluid culture will be added and charged separately. If chorionic villus specimen is received, fibroblast culture will be added and charged separately.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Custom Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing when appropriate

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

VWF Gene, Full Gene NGS

Aliases
Lists additional common names for a test, as an aid in searching

VWD

von Willebrand factor

von Willebrand disease

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

A clinical and laboratory testing algorithm for von Willebrand disease (VWD) has been developed by the National Heart, Lung, and Blood Institute of the National Institutes of Health that is freely available at https://www.nhlbi.nih.gov/health-pro/guidelines/current/von-willebrand-guidelines.

 

The laboratory workup for VWD is complex and requires initial coagulation screening (including a CBC, platelet count, partial thromboplastin time (PTT), prothrombin time (PT), and fibrinogen or thrombin time) should be performed prior to any consideration of genetic testing. Genetic testing should not be performed until a definitive diagnosis of VWD has been made.

 

Prenatal genetic testing is not performed without the prior identification of familial VWF alterations.

 

For any cord blood or prenatal specimen that is received, maternal cell contamination studies will be added. A maternal whole blood sample is required to perform this test.

 

If amniotic fluid is received, amniotic fluid culture will be added and charged separately. If chorionic villus specimen is received, fibroblast culture will be added and charged separately.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Genetic testing should only be considered if clinical and family history, initial coagulation screens, initial von Willebrand factor (VWF) tests (antigen, ristocetin cofactor, and factor VIII coagulant activity), and specialized nongenetic VWF studies indicate a diagnosis of VWD.

Additional Testing Requirements

Due to the complexity of testing non-peripheral blood, consultation with the laboratory is required for all cord blood samples. All cord blood specimens must be accompanied by a maternal blood specimen. Order this test on the cord blood specimen (only 1 sample tube required) and order MATCC / Maternal Cell Contamination, Molecular Analysis, Blood on the maternal specimen.

Shipping Instructions

Prenatal Specimens: Advise Express Mail or equivalent if not on courier service. Prenatal specimens can be sent Monday through Thursday and must be received by 3 p.m. CST on Friday in order to be processed appropriately.

Blood: Ambient and refrigerate specimens must arrive within 7 days and frozen specimens must arrive within 14 days .

Collect and package specimen as close to shipping time as possible.

Necessary Information

von Willebrand Disease Patient Information is required, see Special Instructions. Testing may proceed without the patient information, however, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Results will be reported and also telephoned or faxed, if requested.

 

Submit only 1 of the following specimens:

 

Specimen Type: Peripheral blood or cord blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD) or light-blue top (sodium citrate)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred) 7 days/Refrigerated 7 days/Frozen 14 days

 

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing.

 

Specimen Type: Amniotic fluid

Supplies: Refrigerate/Ambient Mailer, 5 lb (T329)

Container/Tube: Amniotic fluid container

Specimen Volume: 10-20 mL

Collection Instructions:

1. Optimal timing for specimen collection is during 14 to 18 weeks of gestation, but specimens collected at other weeks of gestation are also accepted.

2. Discard the first 2 mL of amniotic fluid.

3. Place the tubes in a Styrofoam container.

4. Fill remaining space with packing material.

5. Unavoidably, about 1% to 2% of mailed-in specimens are not viable.

6. Bloody specimens are undesirable.

7. If the specimen does not grow in culture, you will be notified within 7 days of receipt.

Additional Information:

A separate culture charge will be assessed under CULAF / Amniotic Fluid Culture for Genetic Testing

Specimen Stability Information: Refrigerated (preferred) <24 hours/Ambient <24 hours

 

Specimen Type: Chorionic villi

Supplies: CVS Media (RPMI) and Small Dish (T095)

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20-30 mg

Collection Instructions:

1. Collect specimen by the transabdominal or transcervical method.

2. Transfer the chorionic villi specimen to a Petri dish containing transport medium.

3. Using a stereomicroscope and sterile forceps, assess the quality and quantity of the villi and remove any blood clots and maternal decidua.

Additional Information:

A separate culture charge will be assessed under CULFB / Fibroblast Culture for Genetic Testing

Specimen Stability Information: Refrigerated (preferred) <24 hours/Ambient <24 hours

 

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks approximately 90% confluent

Collection Instructions: Submit confluent cultured cells from another laboratory

Additional Information: There will be no culture charge.

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. von Willebrand Disease Patient Information (T825) is required, see Special Instructions.

2. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

3. If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL

Amniotic fluid: 10 mL

Chorionic villi: 10 mg

Confluent cultured cells: 2 full flasks

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Genetic confirmation of hereditary von Willebrand disease with the identification of alterations in the VWF gene known or suspected to cause the condition

 

Testing for close family members of an individual with a von Willebrand disease diagnosis

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test detects pathogenic alterations within the VWF gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of von Willebrand disease (VWD), a bleeding disorder of variable severity.

 

The gene target for this test includes the following:

Gene name (transcript): VWF (GRCh37 (hg19) NM_000552)

Chromosomal location: 12p13.31

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

A clinical and laboratory testing algorithm for von Willebrand disease (VWD) has been developed by the National Heart, Lung, and Blood Institute of the National Institutes of Health that is freely available at https://www.nhlbi.nih.gov/health-pro/guidelines/current/von-willebrand-guidelines.

 

The laboratory workup for VWD is complex and requires initial coagulation screening (including a CBC, platelet count, partial thromboplastin time (PTT), prothrombin time (PT), and fibrinogen or thrombin time) should be performed prior to any consideration of genetic testing. Genetic testing should not be performed until a definitive diagnosis of VWD has been made.

 

Prenatal genetic testing is not performed without the prior identification of familial VWF alterations.

 

For any cord blood or prenatal specimen that is received, maternal cell contamination studies will be added. A maternal whole blood sample is required to perform this test.

 

If amniotic fluid is received, amniotic fluid culture will be added and charged separately. If chorionic villus specimen is received, fibroblast culture will be added and charged separately.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

von Willebrand disease (VWD) is a bleeding diathesis that usually involves mucous membranes and skin sites. It is typically of mild to moderate severity, although life-threatening bleeding in the central nervous system or gastrointestinal (GI) tract can occur. The most common presenting symptoms in individuals affected by VWD include epistaxis, menorrhagia, bleeding after dental extraction, postoperative bleeding, ecchymoses, bleeding from minor cuts or abrasions, gingival bleeding, and hemarthrosis.(1)

 

VWD affects up to 1% of the general population. While VWD occurs with equal frequency among men and women, symptoms in women are more obvious because of increased bleeding during menstrual periods, pregnancy, and after childbirth.

 

VWD is a result of defects in the concentration, structure, or function of von Willebrand factor (VWF), leading to decreased factor VIII (FVIII) in circulation and/or impaired platelet adhesion and aggregation at the site of vascular injury. The VWF gene encodes for VWF, a protein that protects blood clotting FVIII from degradation in circulation and promotes platelet adhesion and aggregation at the site of vascular injury. In circulation, VWF assembles into linear strings called multimers, the size of which is biologically important, larger multimers being more reactive than smaller multimers.

 

In general, bleeding risk is typically proportional to severity of VWF deficiency or the degree to which it impairs VWF function. However, bleeding risk is highly variable in von Willebrand due to the complexity of the protein structure and function and the great heterogeneity in alteration types that cause this disease. Further, because VWD is an autosomal gene, biallelic combinations of different sequence variants also contribute to phenotypic variability.

 

VWD is classified into 3 types:

Type 1- Partial quantitative deficiency of VWF

Type 2- Qualitative VWF defects including

-Type 2A-Decreased VWF-dependent platelet adhesion and a selective deficiency of high-molecular-weight VWF multimers,

-Type 2B-Increased affinity for platelet glycoprotein Ib

-Type 2M-Decreased VWF-dependent platelet adhesion without a selective deficiency of high-molecular-weight VWF multimers

-Type 2N-Markedly decreased binding affinity for factor VIII

Type 3- Virtually complete deficiency of VWF

 

VWD type 1 and type 2B are inherited in an autosomal dominant manner. VWD type 2A and 2M have been observed to be inherited in both autosomal dominant or autosomal recessive manners. VWD type 2N and 3 are inherited in an autosomal recessive manner.

 

Causes of acquired (nongenetic) VWD that should be excluded prior to genetic testing include:

1) Autoimmune clearance of inhibition of VWF, typically in association with lymphoproliferative diseases, monoclonal gammopathies, systemic lupus erythematosus, and some cancers

2) Increased shear-induced proteolysis of VWF, which can occur with cardiovascular lesions or with pulmonary hypertension

3) Increased binding of VWF to platelets and other cell surfaces, associated with myeloproliferative disorders

4) Nonimmune-related hypothyroidism

5) Use of valproic acid, ciprofloxacin, griseofulvin, hydroxyethyl starch, and other drugs.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

 

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics and Genomics (ACMG) recommendations as a guideline. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Consultations with the Mayo Clinic Special Coagulation Clinic, Molecular Hematopathology Laboratory, or Thrombophilia Center are available for DNA diagnosis cases. This may be especially helpful in complex cases or in situations where the diagnosis is atypical or uncertain.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical:

Some individuals may have a mutation that is not identified by the methods performed. The absence of a variant, therefore, does not eliminate the possibility of von Willebrand disease (VWD). This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies (VAF) significantly lower than 50%. Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

Technical Limitations:

Next-generation sequencing (NGS) may not detect all types of genetic variants. Additionally, rare alterations may be present that could lead to false negative or positive results. Therefore test results should be interpreted in the context of activity and antigen measurements, clinical findings, family history, and other laboratory data. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If multiple alterations are identified, NGS is not able to distinguish between alterations that are found in the same allele ("in cis") and alterations found on different alleles ("in trans"). This limitation may complicate diagnosis or classification and has implications for inheritance and genetic counseling. To resolve these cases, molecular results must be correlated with clinical history, activity and antigen measurements, and family studies.

 

Unless reported or predicted to cause disease, alterations found deep in the intron or alterations that do not result in an amino acid substitution are not reported. These and common polymorphisms identified for this patient are available upon request.

 

Reclassification of Variants Policy:

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

 

Contact the laboratory if additional information is required regarding the transcript and/or human genome assembly used for the analysis of this patient's results.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Nichols WL, Hultin MB, James AH, et al: von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia. 2008;14(2):171-232

2. Goodeve AC: The genetic basis of von Willebrand disease. Blood Rev 2010;24(3):123-134

3. Springer TA: von Willebrand factor, Jedi knight of the bloodstream. Blood 2014;124(9):1412-1425

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing and/or Sanger sequencing are performed.

 

Regions of homology, high guanine-cytosine (GC)-rich content, and repetitive sequences may not provide accurate sequence. Therefore, all reported alterations detected by next-generation sequencing in these regions are confirmed by an independent reference method. However, this does not rule out the possibility of a false-negative result in these regions.

 

Sanger sequencing is used to confirm alterations detected by next-generation sequencing when appropriate. (Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

21 to 28 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks; DNA: Indefinitely

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81408

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
VWFNG VWF Gene, Full Gene NGS 94219-3
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
113117 VWFNG Result 50397-9
113111 Alterations Detected 82939-0
113109 Interpretation 69047-9
113112 Additional Information 48767-8
113113 Method 85069-3
113114 Disclaimer 62364-5
113116 Reviewed By 18771-6
113115 Panel Gene List 40970-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports