Which CPT Codes are Used in Pharmacogenetic (PGx) Testing Billing?

The CPT codes used in pharmacogenetic (PGx) testing billing are mostly single-gene molecular pathology codes, one per gene, with a growing set of lab-specific PLA codes for branded panels. Which ones a lab can bill, and which ones a payer will actually pay, depends on the genes that were clinically needed for the drug decision in front of the prescriber.

Key Takeaways

Single-Gene PGx Codes

Most PGx testing bills under Tier 1 molecular pathology codes. Each code describes one gene and the common variants for it, and the lab reports one unit per gene tested. The drug in parentheses is the kind of prescribing decision that usually supports coverage.

Warfarin genotyping is the usual example of stacking. CYP2C9 (81227) and VKORC1 (81355) are billed together when both are tested for the same dosing decision. Medicare treats warfarin genotyping under a national coverage determination that limits payment to clinical study settings, so most warfarin PGx claims to Medicare deny no matter how they’re coded.

Medicare also sets medically unlikely edits on these codes, usually one unit per gene per day. Billing a gene twice, or billing the same gene again after it was already tested, gets cut automatically. If you’re unsure which code describes a test, our guide on how to choose the correct CPT code walks through the general process.

Panel Codes and PLA Codes

CPT has no general code for a PGx panel by gene count. A lab running a multigene panel has three options, and the right one depends on the test itself.

The first is a Proprietary Laboratory Analyses code. PLA codes describe one lab’s specific test, and when a test has one, the lab has to use it instead of stacking single-gene codes. Examples include 0029U (Mayo Clinic’s focused pharmacogenomics panel), 0030U (Mayo Clinic’s warfarin response panel), and 0345U (the GeneSight psychotropic panel). The AMA adds new PLA codes every quarter, so the code set changes often.

The second is stacking the individual Tier 1 codes, one for each gene. Payers then review each gene on its own, and the ones without a current drug decision behind them deny.

The third is 81479, the unlisted molecular pathology code, for genes or methods that no specific code describes. Unlisted claims need a description of the test and usually go to manual review, so payment is slower and less predictable.

Exome and Genome Sequencing

PGx results sometimes come from broader sequencing done for another reason. Those tests bill under their own codes, and the PGx findings don’t add a separate charge.

Payers cover exome and genome sequencing under their own genetic testing criteria, usually for suspected genetic disorders, not for PGx alone. A lab can’t bill whole exome sequencing to get PGx results that a targeted test would have produced.

MolDX, Z-Codes, and Diagnosis Codes

Most Medicare contractors process molecular testing through the MolDX program. Each test has to be registered in the DEX Diagnostics Exchange, and the Z-code it receives goes on every Medicare claim alongside the CPT code. MolDX covers PGx testing when the patient is being considered for a drug with a known gene-drug interaction and the result will change the drug or dose.

The diagnosis on the claim should be the condition being treated, such as major depressive disorder, atrial fibrillation, or colorectal cancer. Long-term drug therapy codes from the Z79 category can support the claim when the patient is already on the medication. Claims sent with only a screening or family history code rarely meet medical necessity for PGx.

Gene-drug pairs with FDA labeling or CPIC guidelines carry the most weight on review and appeal. When a payer denies a gene with strong guideline support, the ordering note and the guideline are usually what overturn it.

Common PGx Billing Problems

The biggest one is preemptive panel testing. A panel ordered for a patient with no current prescribing decision is denied by Medicare and most commercial plans, even when every code on it is correct.

The second is authorization that doesn’t match the claim. Many commercial plans require prior authorization for genetic testing, often through a lab benefit manager, and the approval lists specific codes. A lab that bills more genes than were approved gets the extra codes denied.

The third is billing the wrong entity. The performing lab bills the test. The ordering practice doesn’t bill for the test or for collecting a cheek swab, and independent labs bill the Medicare contractor for the state where the lab is located, not where the patient lives.

Patients also get surprised by the bill. When a test may not meet Medicare coverage criteria, the lab needs a signed Advance Beneficiary Notice before testing and bills with the GA modifier. Without it, the lab can’t bill the patient if the claim denies.

Labs looking for the full picture on PGx coverage, credentialing, and lab enrollment can see our PGx testing billing and credentialing page.

PGx CPT Code FAQs

Getting PGx Claims Paid With Medwave

Medwave codes PGx claims gene by gene against the order, checks for a PLA code before anything is stacked, and confirms the Z-code and authorization match before the claim leaves. Denied genes go back out with the ordering note and the guideline for that gene-drug pair.

If your lab is seeing panel reductions or MolDX denials, send us a few recent remits through the form below and we’ll tell you which codes are causing them.

Alex J. Lau

Co-Founder and COO of Medwave, bringing more than 25 years of hands-on experience in healthcare revenue cycle management, payer contracting, and medical credentialing.