Invitae Chronic Pancreatitis Panel


Test description

The Invitae Chronic Pancreatitis Panel analyzes five genes that are associated with an increased risk of chronic pancreatitis (CP), a condition that results in irreversible morphological changes and impairment of both exocrine and endocrine functions. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive test for chronic pancreatitis.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (5 genes)


CFTR: Analysis includes the intronic variants: NM_000492.3:c.3718-2477C>T (also known as 3849+10kbC>T), c.1210-34TG[12]T[5] (also known as T5TG12), c.1210-34TG[11]T[5] (also known as T5TG11), and c.1679+1634A>G.

  • Chronic pancreatitis

The pancreas is responsible for synthesizing enzymes for protein, fat, and carbohydrate digestion in the intestines and for producing insulin and glucagon for maintaining blood-sugar balance. Chronic pancreatitis is a progressive inflammatory disorder in which overly active digestive enzymes destroy the pancreatic secretory cells. The primary features of chronic pancreatitis include intractable pain and maldigestion, followed by diabetes mellitus and malnutrition with advancing disease.

Alcoholism is the leading cause of chronic pancreatitis and accounts for approximately 50% of all cases worldwide. Approximately 10% of cases with alcoholic chronic pancreatitis (ACP) have been found to have a pathogenic variant in one of these genes, and pathogenic variants in these genes have been identified in approximately 90% of individuals with idiopathic (previously unexplained) chronic pancreatitis (ICP).

The inheritance pattern of chronic pancreatitis varies by gene:

  • CASR, CFTR, and CTRC – increased risk
  • PRSS1 –- autosomal dominant
  • SPINK1 –- autosomal recessive

CFTR is also known to cause autosomal recessive cystic fibrosis (CF) and congenital bilateral absence of vas deferens (CBAVD).

  • Gain-of-function mutations (pathogenic missense and copy number variants) in PRSS1 have an 80% penetrance.
  • Loss-of-function mutations (pathogenic splicing and truncating variants) in PRSS1 may have a protective effect against the development of chronic pancreatitis, but the penetrance of this effect is unknown.
  • Loss-of-function mutations (pathogenic splicing and truncating variants) in SPINK1 have a penetrance of 30%–75%, depending on the mutation.
  • Loss-of-function mutations (pathogenic missense, splicing, and truncating variants) in CASR, CFTR, and CTRC have low penetrance. Pathogenic variants in these genes have been shown to increase the risk of chronic pancreatitis between two- and tenfold, depending on the variant.

The prevalence of chronic pancreatitis is ~1 in 4,000 on average, with considerably higher rates (~1 in 1000) in southern India.

Testing for chronic pancreatitis may be considered in any individual with a personal and/or family history of:

  • unexplained episodes of acute pancreatitis in childhood
  • recurrent acute attacks of pancreatitis of unknown cause
  • chronic pancreatitis of unknown cause, particularly with onset before age 25 years
  • signs and symptoms of pancreatitis-associated syndromes, such as cystic fibrosis (CF) or atypical CF

  1. Bellin, MD, et al. Total pancreatectomy and islet autotransplantation in chronic pancreatitis: recommendations from PancreasFest. Pancreatology. 2014; 14(1):27-35. PMID: 24555976
  2. Braganza, JM, et al. Chronic pancreatitis. Lancet. 2011; 377(9772):1184-97. PMID: 21397320
  3. Chen, JM, Férec, C. Chronic pancreatitis: genetics and pathogenesis. Annu Rev Genomics Hum Genet. 2009; 10:63-87. PMID: 19453252
  4. Ellis, I, et al. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues. Pancreatology. 2001; 1(5):405-15. PMID: 12120217
  5. Ellis, I. Genetic counseling for hereditary pancreatitis--the role of molecular genetics testing for the cationic trypsinogen gene, cystic fibrosis and serine protease inhibitor Kazal type 1. Gastroenterol. Clin. North Am. 2004; 33(4):839-54. PMID: 15528021
  6. Etemad, B, Whitcomb, DC. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology. 2001; 120(3):682-707. PMID: 11179244
  7. LaRusch, J, et al. Pancreatitis Overview. 2014 Mar 13. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 24624459
  8. Rickels, MR, et al. Detection, evaluation and treatment of diabetes mellitus in chronic pancreatitis: recommendations from PancreasFest 2012. Pancreatology. 2013; 13(4):336-42. PMID: 23890130
  9. Solomon, S, Whitcomb, DC. Genetics of pancreatitis: an update for clinicians and genetic counselors. Curr Gastroenterol Rep. 2012; 14(2):112-7. PMID: 22314809
  10. Solomon, S, et al. PRSS1-Related Hereditary Pancreatitis. 2012 Mar 01. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 22379635
  11. Witt, H, et al. Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology. 2007; 132(4):1557-73. PMID: 17466744

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CASR NM_000388.3
CFTR* NM_000492.3
CTRC NM_007272.2
PRSS1 NM_002769.4
SPINK1 NM_003122.4

CFTR: Analysis includes the intronic variants: NM_000492.3:c.3718-2477C>T (also known as 3849+10kbC>T), c.1210-34TG[12]T[5] (also known as T5TG12), c.1210-34TG[11]T[5] (also known as T5TG11), and c.1679+1634A>G.