Test Catalog

Test Id : F12NG

F12 Gene, Next-Generation Sequencing, Varies

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

Genetic confirmation of hereditary angioedema (HAE) type III with the identification of an alteration in the F12 gene known or suspected to cause the condition

 

Testing for close family members of an individual with an HAE type III diagnosis

 

Genetic confirmation of factor XII deficiency with the identification of an alteration in the F12 known or suspected to cause the condition

 

This test is not intended for prenatal 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 in the F12 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of factor XII deficiency or hereditary angioedema with normal C1 inhibitor (FXII-HAE).

 

The gene target for this test is:

Gene name (transcript): F12 (GRCh37 [hg19] NM_000505)

Chromosomal location: 5q35.3

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

Factor XII deficiency:

Special coagulation testing for factor XII should be performed prior to any genetic testing.

 

Genetic testing for factor XII deficiency may be considered if:

-Factor XII activity is reduced (less than 55% of normal)

-Acquired causes of factor XII have been excluded

 

Hereditary angioedema type III (FXII-HAE):

An international consortium has established a testing and diagnostic algorithm for the identification of hereditary angioedema (HAE) type III.(1)

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

F12 Gene, Full Gene NGS

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

Hageman Factor Deficiency

Factor 12 deficiency

F12 deficiency

HFXII-HAE

Type III HAE

HAE with normal C1INH

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

Factor XII deficiency:

Special coagulation testing for factor XII should be performed prior to any genetic testing.

 

Genetic testing for factor XII deficiency may be considered if:

-Factor XII activity is reduced (less than 55% of normal)

-Acquired causes of factor XII have been excluded

 

Hereditary angioedema type III (FXII-HAE):

An international consortium has established a testing and diagnostic algorithm for the identification of hereditary angioedema (HAE) type III.(1)

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Genetic testing for factor XII deficiency typically has little clinical utility. Caution in ordering is advised.

Prior to any genetic testing, factor XII activity should be assessed. Order F_12 / Coagulation Factor XII Activity Assay, Plasma.

 

For hereditary angioedema type III, genetic testing should only be considered when there is a documented family history of angioedema that does not respond to chronic, high-dose antihistamine therapy, normal complement studies, normal C1 inhibitor level and function, and no exposure to medications that could cause angioedema, such as angiotensin-converting enzyme inhibitors or nonsteroidal anti-inflammatory drugs.

Shipping Instructions

Ambient and refrigerated specimens must arrive within 7 days of collection, and frozen specimens must arrive within 14 days.

 

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

Necessary Information

Rare Coagulation Disorder Patient Information is required. 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

Submit only 1 of the following specimens:

 

Specimen Type: Peripheral blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD) or light-blue top (3.2% sodium citrate)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability: Ambient (preferred)/Refrigerated/Frozen

 

Specimen Type: Extracted DNA

Container/Tube: 1.5- to 2-mL tube

Specimen Volume: Entire specimen

Collection Instructions:

1. Label specimen as extracted DNA and source of specimen.

2. Provide indication of volume and concentration of the DNA.

Specimen Stability: Frozen (preferred)/Refrigerated/Ambient

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

Forms

1. Rare Coagulation Disorder Patient Information (T824) is required. Fax the completed form to 507-284-1759.

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:

-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

Extracted DNA: 100 mcL at 50 ng/mcL concentration

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

Gross hemolysis OK
Gross lipemia OK

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 Ambient (preferred) 7 days
Frozen 14 days
Refrigerated 7 days

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

Genetic confirmation of hereditary angioedema (HAE) type III with the identification of an alteration in the F12 gene known or suspected to cause the condition

 

Testing for close family members of an individual with an HAE type III diagnosis

 

Genetic confirmation of factor XII deficiency with the identification of an alteration in the F12 known or suspected to cause the condition

 

This test is not intended for prenatal 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 in the F12 gene to delineate the underlying molecular defect in a patient with a laboratory diagnosis of factor XII deficiency or hereditary angioedema with normal C1 inhibitor (FXII-HAE).

 

The gene target for this test is:

Gene name (transcript): F12 (GRCh37 [hg19] NM_000505)

Chromosomal location: 5q35.3

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

Factor XII deficiency:

Special coagulation testing for factor XII should be performed prior to any genetic testing.

 

Genetic testing for factor XII deficiency may be considered if:

-Factor XII activity is reduced (less than 55% of normal)

-Acquired causes of factor XII have been excluded

 

Hereditary angioedema type III (FXII-HAE):

An international consortium has established a testing and diagnostic algorithm for the identification of hereditary angioedema (HAE) type III.(1)

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

Factor XII (FXII) is a serine protease capable of activating factor VII and factor IX to their active forms but does not appear to significantly contribute to hemostasis. Rather, factor XII activity appears directed more toward inflammatory response through activation of the kallikrein-kinin system .Pathogenic alterations in the F12 gene, which encodes FXII, can cause one of two different phenotypes. Alterations in F12 that reduce the amount of plasma FXII or disrupt its functional activity result in FXII deficiency. Alterations in F12 that disrupt glycosylation or lead to increased contact-mediated autoactivation of zymogen FXII are associated with hereditary angioedema (HAE) type III with normal C1 inhibitor (C1INH).

 

A deficiency of FXII does not cause excessive bleeding tendency or abnormal bleeding even during trauma or surgery despite prolonged partial thromboplastin time (aPTT). Some with severe deficiency experience thrombosis, but a causal connection remains unproven. Individuals with FXII deficiency are generally entirely asymptomatic, making disease state classifications unnecessary. FXII deficiency is inherited in an autosomal recessive manner. Genetic testing for FXII deficiency is generally unnecessary but may be considered if prolonged aPTT and reduced FXII activity is documented and acquired causes of low FXII are excluded. Causes of acquired (nongenetic) FXII deficiency that should be excluded prior to genetic testing include liver disease, nephrotic syndrome, and chronic granulocytic leukemia. A study of 300 healthy blood donors found that 2.3% had FXII deficiency.(2) Actual prevalence of the condition is unknown. Of note, normal, full-term newborn infants or healthy premature infants may have decreased levels (> or =15%-20%) that may not reach adult levels for greater than or equal to 180 days after birth.

 

Defects in F12 that increase contact-mediated FXII autoactivation and lead to excess generation of proinflammatory peptide hormone bradykinin cause HAE type III with normal C1INH. HAE type III is characterized by recurrent skin swelling, abdominal pain attacks, and upper airway obstruction. Symptoms occur almost exclusively in women because estrogen exposure appears to exacerbate the condition and attacks are precipitated or worsened by high estrogen levels. However, not all female patients who carry FXII alterations are symptomatic, thus HAE type III is considered an autosomal dominant disorder with incomplete penetrance. Alterations in F12 are found in 20 to 30% of patient with HAE type III. Genetic testing for HAE type III may be indicated when there is a documented family history of angioedema that does not respond to chronic, high-dose antihistamine therapy, normal complement studies, normal C1INH level and function, and no exposure to medications that could cause angioedema, angiotensin-converting enzyme inhibitors or nonsteroidal antiinflammatory drugs. Of note, acquired causes of angioedema, such as B-cell lymphoproliferative, the presence of autoantibodies to C1 inhibitors, and the use of renin-angiotensin-aldosterone blockers, should be considered and excluded prior to genetic testing of F12 for HAE type III.

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 variant that is not identified by the methods performed. The absence of a variant, therefore, does not eliminate the possibility of factor XII deficiency or hereditary angioedema type III. This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies 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 variants (ie, polymorphisms) may be present that could lead to false-negative or false-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 alterations (ie, 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.

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

1. Bowen T, Cicardi M, Farkas H, et al: 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):24

2. Halbmayer WM, Haushofer A, Schon R, et al: The prevalence of moderate and severe FXII (Hageman factor) deficiency among the normal population: evaluation of the incidence of FXII deficiency among 300 healthy blood donors. Thromb Haemost.. 1994 Jan;71(1):68-72

3. Schmaier AH: The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic actitivies. J Thromb Haemost. 2016 Jan;14(1):28-39

4. Banerji, A: The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2013 Nov;111(5):329-336

5. Björkqvist J, de Maat S, Lewandrowski U, et al: Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III. J Clin Invest. 2015 Aug 3;125(8):3132-3146

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 (NGS) 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 NGS 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 NGS 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.

81479

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
F12NG F12 Gene, Full Gene NGS 94238-3
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.
113068 F12NG Result 50397-9
113062 Alterations Detected 82939-0
113061 Interpretation 69047-9
113063 Additional Information 48767-8
113064 Method 85069-3
113065 Disclaimer 62364-5
113066 Panel Gene List 58902-8
113067 Reviewed By 18771-6

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 | 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