Sign in →

Test Code HPANP Hereditary Pancreatitis Gene Panel, Varies


Ordering Guidance


Patients who have had a previous bone marrow transplant from an allogenic donor should not have testing performed on blood, bone marrow, or saliva because any results generated will reflect the genome of the donor rather than the recipient. Testing on patients who have an active hematologic malignancy or hematologic disorder with clonal proliferation may identify both somatic mutations and germline variants, which may result in test failure or necessitate follow-up testing to determine whether the detected variant is germline or somatic. For these patients, testing a skin biopsy or cultured fibroblasts is recommended. For instructions for testing patients who have received a bone marrow transplant or have an active hematologic disorder, call 800-533-1710. For more information see Cautions.

 

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies. To modify this panel via CGPH, use the Inborn Errors of Immunity/Bone Marrow Failure/Telomeropathy/Pulmonary Fibrosis/Very Early Onset IBD/Pancreatitis disease state for step 1 on the Custom Gene Ordering Tool.

 

Targeted testing for familial variants (also called site-specific or known variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about testing option, call 800-533-1710.



Shipping Instructions


 



Specimen Required


Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For information about testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

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 Information: Ambient (preferred) 4 days/Refrigerated

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

 

Specimen Type: Cord blood

Container/Tube:  Lavender top (EDTA) or yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

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

Specimen Stability Information: Ambient 4 days/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm Punch

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

Additional Information:

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical and Molecular Testing, Tissue. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblasts

Source: Skin

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

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

Additional Information:

1.Specimens are preferred to be received within 24 hours of collection. Culture and/or extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2.A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 2 Swabs

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days

Additional information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.

 

Specimen Type: Extracted DNA

Container/Tube:

Preferred: Screw Cap Micro Tube, 2 mL with skirted conical base

Acceptable: Matrix tube, 1 mL

Collection Instructions:

1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated

Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.


Forms

1. 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)

2. If not ordering electronically, complete, print, and send a Gastroenterology and Hepatology Test Request (T728) with the specimen.

Useful For

Confirming a suspected clinical diagnosis of familial or hereditary pancreatitis in patients with chronic pancreatitis

 

Identifying gene variants contributing to pancreatitis in an individual or family

 

Identifying gene variants to allow for predictive and diagnostic testing in family members

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No
MATCC Maternal Cell Contamination, B Yes No

Testing Algorithm

Skin biopsy:

For skin biopsy or cultured fibroblast specimens, fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

 

Cord blood:

For cord blood specimens that have an accompanying maternal blood specimen, maternal cell contamination studies will be performed at an additional charge.

Method Name

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

Reporting Name

Hereditary Pancreatitis Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Reject Due To

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

Clinical Information

Hereditary pancreatitis (HP) is defined as 2 or more individuals in a family affected with pancreatitis involving at least 2 generations.(1) Variants in several genes, including PRSS1, CFTR, CTRC, and SPINK1 have demonstrated genetic susceptibility to chronic pancreatitis. Disease susceptibility may be monogenic, as is the case with PRSS1, digenic or multigenic, and multifactorial in which multiple genes and environmental factors play a role in disease expression.

 

PRSS1:

The most common monogenic cause of HP is the presence of a variant in the cationic trypsinogen (PRSS1) gene. Variants in the PRSS1 gene are inherited in an autosomal dominant manner. It has been reported that as many as 80% of patients with symptomatic hereditary pancreatitis have a causative PRSS1 variant.(1) HP cannot be clinically distinguished from other forms of pancreatitis. However, PRSS1 variants are generally restricted to individuals with a family history of pancreatitis and are infrequently found in patients with alcohol-induced pancreatitis. Although several variants have been identified, the p.R122H, p.N29I, and p.A16V variants are the most common disease-causing variants in PRSS1 associated with HP.(2) Patients with HP are also at an increased risk for developing pancreatic cancer. Studies have estimated the lifetime risk of developing pancreatic cancer to be as high as 40%.(3)

 

SPINK1:

Biallelic variants in the SPINK1 gene have been associated with increased susceptibility to chronic pancreatitis especially in families without PRSS1 variants; however, it is unknown if biallelic variants alone are sufficient to cause chronic pancreatitis. Additionally, heterozygous SPINK1 variants appear to modify disease severity when observed in combination with variants in other genes.(1,2,4) Unlike PRSS1 variants, SPINK1 variants have been associated with alcohol-induced pancreatitis.(4)

 

CFTR:

Pancreatitis is a known manifestation of an atypical CFTR-related disorder, which results from biallelic disease-causing variants in the CFTR gene. However, CFTR variants can also cooccur with variants in CTRC, SPINK1, or CASR to confer pancreatitis disease susceptibility.(1-4) When observed in the context of a SPINK1 variant, for example, heterozygous variants in CFTR are associated with a 2- to 5-fold increased risk for pancreatitis as compared to the general population.(4)

 

CTRC:

Variants in CTRC have been observed in individuals with chronic pancreatitis in association with other risk factors, such as variants in CFTR or SPINK1 or specific environmental risk factors. Thus, chronic pancreatitis may be attributable to the presence of CTRC variants in the context of other risk factors as opposed to CTRC variants alone.(1)

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(5) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions

Clinical Correlations:

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact Mayo Clinic Laboratories genetic counselors at 800-533-1710.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

 

This analysis targets single and multi-exon deletions/duplications; however, in some instances, single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Genes may be added or removed based on updated clinical relevance. For the most up to date list of genes included in this test and detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent non-leukoreduced blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants:

Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care professionals to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Due to broadening genetic knowledge, it is possible that the laboratory may discover new information of relevance to the patient. Should that occur, the laboratory may issue an amended report.

 

Variant Evaluation:

Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(5) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

 

Rarely, incidental or secondary findings may implicate another predisposition or presence of active disease. These findings will be carefully reviewed to determine whether they will be reported.

Day(s) Performed

Varies

Report Available

28 to 42 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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

CPT Code Information

81223

81404 x2

81405

81479 (if appropriate for government payers)

88223- Tissue culture, skin, solid tissue biopsy (if appropriate)

88240- Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HPANP Hereditary Pancreatitis Gene Panel 22070-7

 

Result ID Test Result Name Result LOINC Value
619845 Test Description 62364-5
619846 Specimen 31208-2
619847 Source 31208-2
619848 Result Summary 50397-9
619849 Result 82939-0
619850 Interpretation 69047-9
619851 Additional Results 82939-0
619852 Resources 99622-3
619853 Additional Information 48767-8
619854 Method 85069-3
619855 Genes Analyzed 82939-0
619856 Disclaimer 62364-5
619857 Released By 18771-6