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Colorectal Cancer Predisposition via the POLD1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
POLD1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7509POLD181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Yuan Xue, PhD

Clinical Features and Genetics

Clinical Features

Colorectal cancer (CRC) is the development of tumors in the colon and rectum that occur in approximately 8% of individuals with cancer (Siegel et al. 2015). Similar to other cancers, CRC is caused by genetic and environmental factors (e.g. smoking, diet). Approximately 30% of CRCs are considered familial and 5% of CRCs are caused by a Mendelian disorder (Esteban-Jurado 2014). Colorectal cancer is generally broken down into the presence or absence of polyposis (numerous internal polyps). CRC inherited diseases include Lynch syndrome, Familial Adenomatous polyposis, Peutz-Jeghers, Juvenile Polyposis and Cowden syndrome. A recent syndrome has been coined CRC-polymerase proofreading-associated polyposis (PPAP). It is caused by pathogenic variants in proofreading DNA repair genes (Palles et al. 2012). Mutations in these genes predispose individuals to adenomatous polyposis or early-onset cancer (Spier et al. 2015). Identification of pathogenic variants in the germline of CRC patients is important for cancer surveillance (i.e. colonoscopy) for the affected individual and family members, since early surveillance and treatment has been shown to decrease morbidity and mortality (Kohlmann and Gruber 2014).


Colorectal predisposition syndrome is inherited in an autosomal dominant manner. Polymerase proofreading associated polymerase (PPAP) is caused by pathogenic variants in two proofreading DNA repair genes POLD1 and POLE (Chubb et al. 2015). The protein products of these genes are involved in the replication of DNA and are also involved in DNA repair. POLE synthesizes the leading strand, while POLD synthesizes Okazaki fragments of the lagging strand. Mutations in the proof-reading exonuclease domains of these proteins result in the inability to correct mismatched bases during DNA replication. Pathogenic variants in the POLD1 gene result in predisposition to colorectal and endometrial cancer (Church et al. 2013). Tumors from individuals with these pathogenic variants are microsatellite stable, but acquire base substitution mutations (Palles et al. 2012). Reported pathogenic variants in POLD1 only include missense variants (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the POLD1 gene have been observed in 0.2% of individuals with colorectal cancer (Chubb et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the POLD1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

This test is suitable for individuals with multifocal, recurrent, and early onset (e.g. < 50 years) colorectal and endometrial tumors or a family history of these tumors. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.


Official Gene Symbol OMIM ID
POLD1 174761
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Colorectal cancer, susceptibility to, 10 AD 612591

Related Test

Hereditary Endometrial Cancer Panel


  • Chubb D, Broderick P, Frampton M, Kinnersley B, Sherborne A, Penegar S, Lloyd A, Ma YP, Dobbins SE, Houlston RS. 2015. Genetic Diagnosis of High-Penetrance Susceptibility for Colorectal Cancer (CRC) Is Achievable for a High Proportion of Familial CRC by Exome Sequencing. Journal of Clinical Oncology 33: 426–432. PubMed ID: 25559809
  • Church DN, Briggs SEW, Palles C, Domingo E, Kearsey SJ, Grimes JM, Gorman M, Martin L, Howarth KM, Hodgson SV, The NSECG Collaborators, Kaur K, Taylor J, Tomlinson IP. 2013. DNA polymerase and exonuclease domain mutations in endometrial cancer. Human Molecular Genetics 22: 2820–2828. PubMed ID: 23528559
  • Esteban-Jurado C. 2014. New genes emerging for colorectal cancer predisposition. World Journal of Gastroenterology 20: 1961. PubMed ID: 24587672
  • Human Gene Mutation Database (Bio-base).
  • Kohlmann W, Gruber SB. 2014. Lynch Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301390
  • Palles C, Cazier J-B, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Almeida EG, Salguero I, Sherborne A, Chubb D, Carvajal-Carmona LG, Ma Y, Kaur K, Dobbins S, Barclay E, Gorman M, Martin L, Kovac MB, Humphray S; CORGI Consortium; WGS500 Consortium, Lucassen A, Holmes CC, Bentley D, Donnelly P, Taylor J, Petridis C, Roylance R, Sawyer EJ, Kerr DJ, Clark S, Grimes J, Kearsey SE, Thomas HJ, McVean G, Houlston RS, Tomlinson I. 2012. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nature Genetics 45: 136–144. PubMed ID: 23263490
  • Siegel RL, Miller KD, Jemal A. 2015. Cancer statistics, 2015: Cancer Statistics, 2015. CA: A Cancer Journal for Clinicians 65: 5–29. PubMed ID: 25559415
  • Spier I, Holzapfel S, Altmüller J, Zhao B, Horpaopan S, Vogt S, Chen S, Morak M, Raeder S, Kayser K, Stienen D, Adam R, Nürnberg P, Plotz G, Holinski-Feder E, Lifton RP, Thiele H, Hoffmann P, Steinke V, Aretz S. 2015. Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas: POLE Mutations in Polyposis. International Journal of Cancer n/a–n/a. PubMed ID: 25529843


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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