Summary & Overview
CPT 0486U: Methylation-Based ctDNA Tumor Fraction Assay
CPT code 0486U designates a Proprietary Laboratory Analyses (PLA) test for Northstar Response™, a laboratory-developed assay from BillionToOne Laboratory that uses next-generation sequencing to quantify methylation markers in cell-free circulating tumor DNA (ctDNA) across pan–solid tumors. The test reports a methylation-based correlate of tumor fraction, providing a tumor-derived signal from a blood specimen. Nationally, PLA codes like 0486U matter because they identify manufacturer- or laboratory-specific diagnostics that can influence coverage, coding consistency, and price transparency for advanced molecular tests.
Key payers included in this analysis are Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the clinical purpose and laboratory setting for the test, an explanation of payer relevance, and what to expect in payer coverage discussions for PLA-coded molecular diagnostics. The publication summarizes typical sites of service, common modifiers reported with PLA tests, and where to locate clinical context for methylation-based ctDNA assays. It also outlines the national policy implications of PLA codes for access and claims processing, and describes the types of benchmarks and policy updates that are relevant for laboratories, clinicians, and payers evaluating novel molecular diagnostics.
Billing Code Overview
CPT code 0486U is a Proprietary Laboratory Analyses (PLA) code that applies to a single, manufacturer-specific laboratory test: Northstar Response™ from BillionToOne Laboratory, BillionToOne Inc. The test uses next-generation sequencing to analyze methylation markers in cell-free circulating tumor DNA (ctDNA) from pan–solid tumors and produces a quantitative measurement of methylation as a correlate of tumor fraction (the proportion of ctDNA relative to total cell-free DNA in the sample).
Service type: Laboratory molecular diagnostic test using next-generation sequencing for methylation analysis of cell-free DNA
Typical site of service: Clinical laboratory or reference laboratory; specimen collected in an outpatient phlebotomy or other ambulatory collection setting
Data not available in the input for associated taxonomies, ICD-10 diagnoses, and related codes.
Clinical & Coding Specifications
Clinical Context
A 62-year-old patient with a known history of metastatic non–small cell lung cancer under systemic therapy presents for interval surveillance. Their oncology team orders Northstar Response™ to quantify tumor-derived circulating cell-free DNA methylation fraction from a peripheral blood draw to assess tumor fraction trends and potential molecular response. Blood is collected in a cfDNA-preserving tube during an outpatient oncology clinic visit or phlebotomy suite. The specimen is sent to BillionToOne Laboratory for next-generation sequencing–based methylation analysis. Results reporting provides a quantitative methylation-derived tumor fraction that the treating oncologist integrates with imaging, clinical exam, and laboratory results to inform assessment of treatment response and consideration of further diagnostic or therapeutic steps. Typical site of service: outpatient clinic, hospital outpatient department, or commercial reference laboratory processing.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
00 | Not a valid modifier for Medicare; placeholder proprietary modifier in some systems | Rarely used; not typically appended for this PLA code unless system requires a default modifier |
22 | Increased procedural services |