Test Catalog

Test Id : PRCNG

PROCR Gene, Next-Generation Sequencing, Varies

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

Ascertaining a pathogenic alteration in the PROCR gene in patients with recurrent unprovoked venous thromboembolism (VTE)before the age of 40, a strong family history of unexplained and unprovoked VTE, and prior genetic testing for more common genetic variants associated with thrombophilia that does not correlate with the severity of the patient’s thrombophilia or clinical presentation

 

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 alterations in the PROCR gene associated with increased risk for venous thromboembolism.

 

The gene target for this test is:

Gene name (transcript): PROCR (GRCh37 [hg19] NM_006404)

Chromosomal location: 20q11.22

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

No screening tests exist for defects in PROCR. A set of clinical guidelines from the British Society for Haematology on testing for heritable thrombophilia is freely available.(1) A genetic consultation is strongly recommended prior to ordering PROCR sequencing.

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

PROCR Gene, Full Gene NGS

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

Protein C Receptor

Endothelial Protein C Receptor

EPCR

Heritable thrombophilia

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

No screening tests exist for defects in PROCR. A set of clinical guidelines from the British Society for Haematology on testing for heritable thrombophilia is freely available.(1) A genetic consultation is strongly recommended prior to ordering PROCR sequencing.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Indiscriminate testing for alterations in PROCR or other genes related to coagulation in unselected patients presenting with a first episode of venous thrombosis is not indicated.(1)

 

Routine testing of PROCR for genetic risk factors for thromboembolism is not recommended and may be of limited use in most cases.

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: Whole 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.

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

Ascertaining a pathogenic alteration in the PROCR gene in patients with recurrent unprovoked venous thromboembolism (VTE)before the age of 40, a strong family history of unexplained and unprovoked VTE, and prior genetic testing for more common genetic variants associated with thrombophilia that does not correlate with the severity of the patient’s thrombophilia or clinical presentation

 

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 alterations in the PROCR gene associated with increased risk for venous thromboembolism.

 

The gene target for this test is:

Gene name (transcript): PROCR (GRCh37 [hg19] NM_006404)

Chromosomal location: 20q11.22

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

No screening tests exist for defects in PROCR. A set of clinical guidelines from the British Society for Haematology on testing for heritable thrombophilia is freely available.(1) A genetic consultation is strongly recommended prior to ordering PROCR sequencing.

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

Venous thromboembolism (VTE) can describe:

A deep vein thrombosis (DVT) characterized by leg pain or tenderness typically in only 1 thigh or calf, leg swelling, skin that feels warm to the touch, and reddish discoloration or streaks.

-A pulmonary embolism (PE) characterized by unexplained shortness of breath, rapid breathing, chest pain under the rib cage, fast heart rate, and light headedness or passing out.

 

VTEs affect about an estimated 900,000 individuals in the US per year.(2) While most individuals who experience a VTE do so only once in their life, some individuals may experience recurrent thrombotic episodes or have close relatives who do. The tendency to thrombose, sometimes referred to as thrombophilia or hypercoagulability, is considered a multifactorial disorder with many different factors increasing the risk for abnormal clotting. Thrombophilia is more likely to happen in people who are older, obese or overweight, and have conditions that promote blood coagulation like cancer or lupus. Other causes of acquired (nongenetic) thrombophilia include recent surgery, trauma, fractures, hospital or nursing home confinement, varicose veins, neurological disease with leg paresis, chronic kidney disease, oral contraceptive use and hormone therapy, pregnancy and the postpartum period.(2) Less commonly, certain alterations in genes involved in blood coagulation may also increase the risk for thrombosis. A genetic cause for increased VTE may be considered in situations where a VTE occurs before the age of 40, is recurrent, occurs in multiple closely related family members, and occurs in unusual locations in the body such as the portal, hepatic, mesenteric, or cerebral veins.

 

The PROCR gene encodes for endothelial cell protein C receptor (EPCR), a transmembrane protein that plays a crucial role in the negative regulation of blood coagulation by increasing protein C activation 5- to 20 fold via the thrombin-thrombomodulin complex.(3) Activated protein C (APC) then down regulates thrombin generation by inactivating factor VIIIa and factor Va. Rare alterations in the PROCR gene may increase the risk of thrombosis, especially in carriers of other prothrombotic alterations, by an unknown amount. As a whole, the PROCR gene and alterations in it are not well characterized and thus genetic testing has limited clinical utility. As of January 2019, only 3 missense alterations and a single nucleotide variant (SNV) in the 5' untranslated region (5'UTR) in PROCR are reported to be associated with increased risk for venous thromboembolism in the Human Gene Mutation Database (HGMD Professional 2018.4). The prevalence of individuals with pathogenic alterations in the PROCR gene in the general population or among individuals with VTE is unknown.

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 interpretative 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 an increased risk of venous thromboembolism. 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/or 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. Baglin T, Gray E, Greaves M, et al: Clinical guidelines for testing for heritable thrombophilia. Br J Haematol. 2010 Apr;149(2):209-220

2. Heit JA: The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):370-372

3. Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT: The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA. 1996 Sep 17;93(19):10212-10216

4. Bouwnes EAM, Stavenuiter F, Mosnier LO: Mechanisms of anticoagulant and cytoprotective actions of the protein C pathway. J Thromb Haemost. 2013 Jun;11 Suppl 1(0 1):242-253

5. Nayak RC, Sen P, Ghosh S, et al: Endothelial cell protein C receptor cellular localization and trafficking: potential functional implications. Blood. 2009 Aug 27;114(9):1974-1986

6. Medina P, Navarro S, Estelles A, Espana F: Polymorphisms in the endothelial protein C receptor gene and thrombophilia. Thromb Haemost. 2007 Sep;98(3):564-569

7. Mohan Rao LV, Esmon CT, Pendurthi UR: Endothelial cell protein C receptor: a multiliganded and multifunctional receptor. Blood. 2014 Sep 4;124(10):1553-1562

8. Wu C, Dwivedi DJ, Pepler L, et al: Targeted gene sequencing identifies variants in the protein C and endothelial protein C receptor genes in patients with unprovoked venous thromboembolism. Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2674-2681

9. Gleeson EM, O'Donnell JS, Preston RJS: The endothelial cell protein C receptor: cell surface conductor of cytoprotective coagulation factor signaling. Cell Mol Life Sci. 2012 Mar;69(5):717-726

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
PRCNG PROCR Gene, Full Gene NGS 92993-5
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.
113092 PRCNG Result 50397-9
113086 Alterations Detected 82939-0
113085 Interpretation 69047-9
113087 Additional Information 48767-8
113088 Method 85069-3
113089 Disclaimer 62364-5
113090 Panel Gene List 48018-6
113091 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 | 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