Pharmacogenetic Testing - (0500) — MM 0500 | CIGNA Coverage Update

Cigna modified MM 0500 for pharmacogenetic testing, effective October 16, 2025. Billing teams need to audit their charge capture across 38 CPT codes and one HCPCS code before that date.

Cigna Healthcare updated its pharmacogenetic testing coverage policy under policy code MM 0500, affecting a broad range of molecular diagnostic codes — from single-gene assays like CPT 81225 (CYP2C19) and 81227 (CYP2C9) to large genomic panel codes like CPT 0516U (40-gene pharmacogenomic panel) and 0347U through 0350U (multi-condition drug metabolism panels). If your lab or practice bills for psychiatric pharmacogenomics, warfarin metabolism testing, or drug-gene interaction panels, this update touches your revenue cycle directly. The Cigna pharmacogenetic testing coverage policy now also cross-references its oncology molecular testing policy for cancer-related indications, so the scope of what's governed here is narrower than it looks — but no less complex.

Quick-Reference Table

Cigna Pharmacogenetic Testing Coverage Criteria and Medical Necessity Requirements 2025

The core of the MM 0500 Cigna system is straightforward: every code in this policy is "Considered Medically Necessary when criteria in the applicable section are met." That sounds simple. It isn't.

Cigna doesn't publish a single blanket standard for all pharmacogenetic tests. Each code — or group of codes — ties to specific clinical criteria. Medical necessity for CPT 81225 (CYP2C19 gene analysis, used in clopidogrel and antidepressant dosing) depends on the clinical scenario driving the test. The same is true for CPT 81328 (SLCO1B1, statin-induced myopathy risk) and CPT 81355 (VKORC1, warfarin metabolism).

Warfarin-related testing gets its own code: HCPCS G9143 covers warfarin responsiveness testing by genetic technique. This code appears specifically in the MM 0500 policy, and it's medically necessary only when Cigna's criteria for that indication are met. CPT 0030U — a more targeted warfarin drug response panel covering CYP2C9, CYP4F2, and VKORC1 — also falls under this policy with the same condition-specific gatekeeping.

The psychiatric pharmacogenomics cluster is the highest-volume billing risk in this update. Codes 0173U, 0175U, 0345U, 0392U, 0411U, 0419U, 0423U, 0437U, 0476U, and 0477U all cover genomic panels for depression, anxiety, and ADHD. Cigna covers these when criteria are met — but documentation must satisfy Cigna's medical necessity criteria for each applicable code per the policy. If your ordering providers aren't documenting why a psychiatric genomic panel is indicated, your claim denial rate on these codes will climb.

Oncology pharmacogenomic codes — CPT 0460U and 0461U — are in MM 0500, but Cigna explicitly directs oncology and hematology pharmacogenetic testing to its separate "Molecular and Proteomic Diagnostic Testing for Hematology and Oncology Indications" policy for additional information. Before billing 0460U or 0461U for oncology indications, verify which policy governs reimbursement for that specific patient's indication.

The ICD-10-CM codes G35.A- and G35.D (multiple sclerosis) appear in the policy data, signaling that MS-related pharmacogenomic testing has a defined place within MM 0500. If you're billing pharmacogenomic tests for MS patients on disease-modifying therapies, document the MS diagnosis with the appropriate G35 code.

Cigna Pharmacogenetic Testing Exclusions and Non-Covered Indications

The policy data doesn't list specific "not covered" exclusions by code — but that's not the same as open coverage. Every code in MM 0500 is gated by selection criteria. A test ordered outside those criteria defaults to not medically necessary under this coverage policy. That means denial.

The real risk is the multi-gene panel codes: 0347U, 0348U, 0349U, and 0350U cover multi-condition drug metabolism panels. Cigna won't cover these as routine or exploratory screens. The clinical justification must connect specific gene targets to medications the patient is currently taking or about to start.

CPT 0456U (rheumatoid arthritis, NGS gene expression, 19 genes) and CPT 0516U (40-gene pharmacogenomic panel) are also in this policy. Both require clear indication-specific documentation. Without it, expect denial.

Coverage Indications at a Glance

Cigna Pharmacogenetic Testing Billing Guidelines and Action Items 2025

CPT, HCPCS, and ICD-10 Codes for Pharmacogenetic Testing Under MM 0500

Covered CPT Codes (When Selection Criteria Are Met)

Covered HCPCS Codes (When Selection Criteria Are Met)

Key ICD-10-CM Diagnosis Codes