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Official Description

TPMT (thiopurine S-methyltransferase) (eg, drug metabolism), gene analysis, common variants (eg, *2, *3)

© Copyright 2025 American Medical Association. All rights reserved.

Common Language Description

The CPT® Code 81335 pertains to the gene analysis of the thiopurine S-methyltransferase (TPMT) gene, specifically focusing on common variants such as *2 and *3. The TPMT gene is crucial as it encodes the enzyme thiopurine S-methyltransferase, which is responsible for the S-methylation process of certain compounds that metabolize thiopurine drugs. These drugs are often utilized in medical treatments that require immune suppression, including conditions like acute lymphoblastic leukemia (ALL), inflammatory bowel disease, various rheumatic disorders, and in the context of organ transplantation. The TPMT gene is situated on the short arm of chromosome 6 at position 22.3, and its analysis is vital for identifying genetic variants that may influence an individual's response to thiopurine medications. The significance of this gene analysis lies in its ability to predict the risk of severe adverse effects associated with thiopurine therapy, particularly bone marrow toxicity and myelosuppression. There are four primary variant alleles that account for over 95% of cases with reduced TPMT enzyme activity: TPMT*2 (238G>C), TPMT*3A (460G>A or 719A>G), TPMT*3B (460G>A), and TPMT*3C (719A>G). Individuals with two normal alleles (TPMT*1) are generally at a low risk for drug toxicity, while those with one variant allele may experience decreased enzyme activity, necessitating a potential reduction in drug dosage. Conversely, individuals possessing two variant alleles face a significantly heightened risk for severe side effects due to minimal or absent enzyme activity. The analysis is performed on samples obtained from blood or buccal cells, which are processed using polymerase chain reaction (PCR) amplification techniques combined with single nucleotide primer extension (SNPE) and fluorescence observation to accurately identify these genetic variants.

© Copyright 2025 Coding Ahead. All rights reserved.

1. Indications

The gene analysis for the thiopurine S-methyltransferase (TPMT) gene is indicated for the following conditions:

  • Acute Lymphoblastic Leukemia (ALL) - This condition often requires the use of thiopurine drugs for treatment, making TPMT testing essential to assess the risk of toxicity.
  • Inflammatory Bowel Disease - Patients undergoing thiopurine therapy for inflammatory bowel disease may benefit from TPMT testing to prevent adverse drug reactions.
  • Rheumatic Conditions - Individuals with rheumatic disorders who are prescribed thiopurine medications should be tested to evaluate their risk for severe side effects.
  • Organ Transplants - TPMT analysis is crucial for transplant recipients receiving thiopurine drugs to ensure safe and effective immunosuppression.

2. Procedure

The procedure for conducting the TPMT gene analysis involves several key steps:

  • Sample Collection - A blood or buccal cell sample is obtained from the patient. This sample collection is a separate reportable procedure and is essential for the subsequent analysis.
  • DNA Extraction - The collected sample undergoes a process of DNA extraction to isolate the genetic material necessary for testing.
  • Polymerase Chain Reaction (PCR) Amplification - The extracted DNA is subjected to PCR amplification, a technique that allows for the replication of specific DNA segments, making it easier to analyze the TPMT gene variants.
  • Single Nucleotide Primer Extension (SNPE) - Following amplification, the SNPE method is employed to identify specific nucleotide changes in the TPMT gene, which correspond to the common variants.
  • Fluorescence Observation - The final step involves fluorescence observation, where the results of the SNPE are analyzed to determine the presence of the TPMT gene variants, providing insight into the patient's metabolic capacity for thiopurine drugs.

3. Post-Procedure

After the TPMT gene analysis is completed, the results are interpreted to assess the patient's risk for thiopurine drug toxicity. Patients with two normal alleles (TPMT*1) are generally considered to have a low risk for adverse effects, while those with one variant allele may require dosage adjustments. Individuals with two variant alleles are at a significantly increased risk for severe side effects, including bone marrow toxicity and myelosuppression, and may need alternative treatment strategies. It is essential for healthcare providers to discuss the results with patients and consider them when planning treatment regimens involving thiopurine medications.

Short Descr TPMT GENE COM VARIANTS
Medium Descr TPMT GENE ANALAYSIS COMMON VARIANTS
Long Descr TPMT (thiopurine S-methyltransferase) (eg, drug metabolism), gene analysis, common variants (eg, *2, *3)
Status Code Statutory Exclusion (from MPFS, may be paid under other methodologies)
Global Days XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC) 9 - Not Applicable
Multiple Procedures (51) 9 - Concept does not apply.
Bilateral Surgery (50) 9 - Concept does not apply.
Physician Supervisions 09 - Concept does not apply.
Assistant Surgeon (80, 82) 9 - Concept does not apply.
Co-Surgeons (62) 9 - Concept does not apply.
Team Surgery (66) 9 - Concept does not apply.
Diagnostic Imaging Family 99 - Concept Does Not Apply
CLIA Waived (QW) No
APC Status Indicator Service Paid under Fee Schedule or Payment System other than OPPS
Type of Service (TOS) 5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS) none
MUE 1
90 Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
59 Distinct procedural service: under certain circumstances, it may be necessary to indicate that a procedure or service was distinct or independent from other non-e/m services performed on the same day. modifier 59 is used to identify procedures/services, other than e/m services, that are not normally reported together, but are appropriate under the circumstances. documentation must support a different session, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same individual. however, when another already established modifier is appropriate it should be used rather than modifier 59. only if no more descriptive modifier is available, and the use of modifier 59 best explains the circumstances, should modifier 59 be used. note: modifier 59 should not be appended to an e/m service. to report a separate and distinct e/m service with a non-e/m service performed on the same date, see modifier 25.
GA Waiver of liability statement issued as required by payer policy, individual case
XU Unusual non-overlapping service, the use of a service that is distinct because it does not overlap usual components of the main service
GZ Item or service expected to be denied as not reasonable and necessary
GW Service not related to the hospice patient's terminal condition
26 Professional component: certain procedures are a combination of a physician or other qualified health care professional component and a technical component. when the physician or other qualified health care professional component is reported separately, the service may be identified by adding modifier 26 to the usual procedure number.
GV Attending physician not employed or paid under arrangement by the patient's hospice provider
GY Item or service statutorily excluded, does not meet the definition of any medicare benefit or, for non-medicare insurers, is not a contract benefit
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2018-01-01 Added Code Added.
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