Summary & Overview

CPT 0481U: IDH1/IDH2/TERT Mutation Analysis, NGS Tumor

CPT code 0481U designates a proprietary next‑generation sequencing (NGS) tumor test from Mayo Clinic that detects mutations in IDH1, IDH2, and TERT. As a PLA code, 0481U applies to a single manufacturer's or laboratory's unique assay and is used to report targeted molecular profiling of tumor specimens to inform diagnosis, prognosis, and potential therapeutic decisions. Nationally, PLA codes like 0481U have relevance for coverage policy, coding consistency, and molecular diagnostics utilization.

Key payers referenced in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find an overview of clinical purpose and test methodology, payer coverage landscape and common modifier usage, and benchmarking context where available. The publication also summarizes coding considerations specific to PLAs, typical sites of service for NGS tumor testing, and implications for claims processing and documentation.

This resource is intended to provide a concise, national‑level summary of the code, its clinical application, and the aspects of payer and billing practice that affect coding, reimbursement, and administrative workflows. Data not available in the input are noted where applicable.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0481UCPTProprietary Laboratory AnalysesNext-Generation SequencingTumor Mutation AnalysisMolecular DiagnosticsIDH1IDH2TERT

Billing Code Overview

CPT code 0481U is a Proprietary Laboratory Analyses (PLA) code for IDH1, IDH2, and TERT Mutation Analysis, Next–Generation Sequencing, Tumor (IDTRT) performed by Mayo Clinic. The test uses next‑generation sequencing to detect single‑nucleotide variants (SNVs), deletions, and insertions in the IDH1, IDH2, and TERT genes from tumor tissue samples.

Service type: Next‑generation sequencing molecular diagnostic assay (tumor mutation analysis)

Typical site of service: Clinical laboratory / hospital laboratory or outpatient specimen collection with laboratory testing performed at the reporting laboratory

Clinical & Coding Specifications

Clinical Context

A patient with a suspected or confirmed central nervous system or other solid tumor undergoes surgical biopsy or resection. Tumor tissue is sent to the Mayo Clinic molecular diagnostics laboratory for next-generation sequencing using the proprietary IDTRT assay (0481U) to detect mutations in IDH1, IDH2, and TERT. Typical indications include molecular characterization of gliomas, other primary brain tumors, or metastatic lesions where identification of IDH1/IDH2 hotspot mutations or TERT promoter mutations will inform diagnostic classification, prognosis, and potential eligibility for targeted therapies or clinical trials. The clinical workflow: tissue is collected in the operating room or interventional suite, fixed or frozen per lab requirements, shipped to the Mayo Clinic laboratory; the lab performs DNA extraction, library preparation, NGS, bioinformatic variant calling for single-nucleotide variants, insertions, and deletions in IDH1, IDH2, and TERT, and returns a molecular pathology report to the ordering neuro-oncologist, neurosurgeon, or oncologist for incorporation into final diagnosis and treatment planning.

Coding Specifications

Taxonomy Code	Specialty	Notes
207RH0000X	Neurological Surgery	Neurosurgeons obtain tumor specimens via resection or biopsy.
207V00000X	Neurology	Neurologists and neuro-oncologists order molecular testing for CNS tumors.
2085P0200X	Medical Oncology	Medical oncologists use results for systemic therapy planning and clinical trial eligibility.
363L00000X	Pathology	Anatomic and molecular pathologists interpret histology and oversee molecular testing.
363A00000X	Clinical Laboratory	Clinical laboratory directors and molecular diagnostics specialists responsible for assay performance and reporting.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C71.9`	Malignant neoplasm of brain, unspecified	Common indication for IDH1/IDH2 and TERT testing in primary brain tumors to refine diagnosis and prognosis.
`C71.0`	Malignant neoplasm of cerebrum, except lobes and ventricles	Location-specific brain tumor code where molecular profiling guides classification and treatment.
`C71.1`	Malignant neoplasm of frontal lobe	Tumor localization code used with molecular testing to inform surgical and adjuvant therapy decisions.
`C79.31`	Secondary malignant neoplasm of brain	For metastatic disease to the brain where molecular profiling may be used to match targeted therapies.
`D33.3`	Benign neoplasm of brain stem	Some indolent or low-grade tumors undergo IDH/TERT testing for classification despite benign behavior on imaging.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88305`	Level IV surgical pathology, gross and microscopic examination	Performed on tumor tissue to provide histologic diagnosis before or alongside molecular testing; guides selection of molecular assays.
`88240`	Flow cytometry, each additional marker (List separately in addition to `88241`)	Occasionally used for hematologic malignancy workup when tissue or cell suspensions are analyzed; complementary to NGS in some tumor types.
`81479`	Unlisted molecular pathology procedure	Used by some labs when no specific molecular code exists; not applicable when `0481U` is the proprietary PLA code used for this specific assay.
`88342`	Immunohistochemistry, per single antibody stain	Used to detect protein expression (e.g., ATRX, p53) that complements IDH/TERT mutation results in tumor classification.
`89049`	Molecular pathology procedure, interpretation and report only (Note: example)	Used in workflows where interpretation-only services are billed separately from technical sequencing; payer rules vary.

`26`	Professional component	Use when reporting only the professional interpretation component separate from the technical laboratory component, if applicable and allowed by the payer.
`TC`	Technical component	Use when reporting only the technical component of testing (laboratory processing and sequencing) when professional interpretation is billed separately.
`QK`	CLIA waived laboratory director modifier	Use when applicable to indicate testing performed under a specific laboratory director arrangement (payer-specific use; follow payer rules).
`QX`	Modifier for CLIA-certified nonphysician practitioner performing test	Use when applicable for lab personnel credentialing distinctions required by some payers.
`QY`	Laboratory performing under arrangement	Use when the performing lab provides services under an arrangement with another lab or entity and payer requires this designator.
`59`	Distinct procedural service (Note: not in provided list)	Data not available in the input.
`52`	Reduced services	Use when the laboratory test was partially reduced or not completed as originally planned.
`53`	Discontinued procedure	Use when testing was started but discontinued for patient- or specimen-related reasons.
`78`	Unplanned return to the operating/procedure room by the same physician following initial procedure	Rare for lab testing; use only if a subsequent surgical specimen is required emergently by the same physician.
`80`	Assistant surgeon	Use when an assistant surgeon was involved in the procedure that obtained the specimen (surgical billing context).
`82`	Assistant not available	Use when a qualified resident or assistant was not available and an assistant surgeon was not used.
`62`	Two surgeons	Use when two surgeons of different specialties performed the operation to obtain the specimen.
`22`	Increased procedural services	Use when the test required significantly greater resources due to specimen complexity or unusual processing.
`52`	Reduced services	Use when testing scope was reduced (duplicate entry consolidated above).