• Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit




Associated disorders

The NTHL1 gene is associated with autosomal recessive NTHL1-associated polyposis (MedGen UID: 902388).

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Invitae tests that include this gene:

The NTHL1 gene encodes a DNA N-glycosylase that is part of the base excision repair machinery responsible for correcting oxidative damage to DNA (PMID: 17923696).

MedGen UID: 902388

Clinical condition
The NTHL1 gene is associated with autosomal recessive NTHL1-associated polyposis (MedGen UID: 902388). NTHL1-associated polyposis is an adult-onset hereditary cancer predisposition syndrome characterized by the development of multiple colonic adenomas, often with progression to colorectal cancer. Other cancer types have also been reported, although data are limited (PMID: 25938944, 26559593, 26431160, 27720914).

Gene information
The NTHL1 gene encodes a DNA N-glycosylase that is part of the base excision repair machinery responsible for correcting oxidative damage to DNA (PMID: 17923696).

NTHL1-associated polyposis has autosomal recessive inheritance, and affected individuals have two pathogenic variants—one in each copy of their NTHL1 genes. Affected individuals will pass one pathogenic NTHL1 variant to all of their children. Both the patient and his/her partner would each have to carry a pathogenic variant in NTHL1 for there to be a risk of NTHL1-associated polyposis in offspring; in this case, the risk of having have an affected child would be 25%.

Medical management and surveillance protocols have been developed by the National Comprehensive Cancer Network (NCCN) for individuals with NTHL1-associated polyposis (NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal. Version 3.2017):

  • Begin colonoscopy at age 25–30 and repeat every 2–3 years if negative.
  • If polyps are found, colonoscopy is recommended every 1–2 years with consideration of surgery if polyp burden becomes unmanageable by colonoscopy.
  • Surgical evaluation is recommended if appropriate.

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.

It is advantageous to know if an individual has pathogenic variants in NTHL1, as medical management recommendations can be implemented. At-risk relatives can be identified, allowing pursuit of a diagnostic evaluation. In addition, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant NTHL1 data are likely to become available in the near future. Awareness of this cancer predisposition encourages patients and their providers to inform at-risk family members, to diligently follow standard screening protocols, and to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information.

Additional reference
Referenced with permission from the NCCN Genetic/Familial High-Risk Assessment: Colorectal. Version 3.2017.© National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed February 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.

The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a statement of consensus of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Review date: March 2018

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
NTHL1 NM_002528.6