ModifiedCentenePolicy N/A

Concert Genetic Testing: Pharmacogenetics

This policy governs coding, example tests, and reimbursement implications for pharmacogenetic (germline) tests used to guide drug therapy and assess drug toxicity risk; it is directed at providers and billing staff submitting claims to Centene/Concert.

Policy Summary

PayerCentene

PolicyConcert Genetic Testing: Pharmacogenetics

Policy CodePolicy N/A

Change TypeOperational and coding updatescriteria reformatted

Effective DateN/A

Next Review DateN/A

Key ActionProviders should reference current professional coding guidance and the Concert Platform for the comprehensive list of registered tests.

SourceLink

POLICY UPDATE CHANGES

Added new PLA CPT codes 0476U, 0477U, 0516U to the policy reference table and separated some PLA codes into separate lines.

Warfarin Sensitivity Analysis Panels clinical criteria reformatted and expanded to allow coverage of small targeted panels for this indication.

Added CPT codes 0423U, 0434U, 0437U, 0438U to the policy coding reference table and criteria for pharmacogenetic panel tests.

Removed certain genes/tests (e.g., SLCO1B1/SLOCIBI) from non-covered lists or policy reference table to align with LCD guidance.

Updated many single-gene variant analysis sections to cite FDA Table of Pharmacogenetic Associations rather than prior sources.

manyexample laboratory tests and panel names listed

Manysingle-gene tests covered with criteria

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Panels investigationalpanels considered investigational

3+new PLA CPT codes added

4new CPT codes added

NCstate applicability

Coverage Criteria and Clinical Policy

General coverage stance

Policy scope and notes on coverage applicability

Pharmacogenetic testing may be used to inform drug selection or evaluate adverse reactions; testing may be performed prior to or during treatment to identify variants that affect drug response or increase risk of toxicity (e.g., sequencing, deletion/duplication, single nucleotide variant testing).

Lists of example tests, laboratories, CPT/PLA codes, and ICD codes are provided for navigation and claims support but are informational only; inclusion or exclusion of any code or test does not guarantee coverage. Providers should reference current professional coding guidance and the Concert Platform for the comprehensive list of registered tests.

Example tests, codes, and indications

Example lists of panels, single-gene tests, associated CPT/proprietary codes, and example ICD codes provided for navigation and claims support.

Example commercial/multi-gene panels enumerated (examples include GeneSight, Professional PGX/Genomind, PGxOne, RightMed/OneOme, Tempus nP, EffectiveRX/GENETWORx, Genomind Pharmacogenetics Report, RightMed Mental Health Gene Report, MyGen Var), often mapped to proprietary PLA/CPT-like codes (examples: 0345U, 81418, 0173U, 0423U, 0419U, 0438U, 0476U, 0477U, 0516U, 0434U).

Example single-gene pharmacogenetic tests listed with representative CPT/PLA mappings and example ICD codes: BCHE (81479), CYP2C9 (81227), CYP2C19 (81225/81479), CYP2D6 (81226), TPMT/NUDT15 (81306, 81335, 0034U, 0169U), UGT1A1 (81350), UGT2B17 (81479), VKORC1 (81355), HLA variants (81379/81380/81381), DPYD (81232). ICD ranges and sample codes (e.g., D00-D49.9, neurologic, psychiatric, oncology, and drug toxicity codes) are provided as examples for claims.

These example tests, laboratories, and codes are illustrative and not exhaustive; see Concert Platform and current coding guidance for authoritative code lists.

Informational mapping only

HLA-B*57:01 variant analysis (81381)

HLA-B*57:01

Medically necessary when the member is being considered for or is currently undergoing treatment with abacavir (e.g., Ziagen).

NAT2 variant analysis (81479)

NAT2

Medically necessary when the member is being considered for or is currently undergoing treatment with amifampridine/amifampridine phosphate (e.g., Firdapse, Ruzurgi).

Investigational for all other indications.

TPMT (81306, 0034U) and NUDT15 (81335, 0169U) variant analyses

TPMT and NUDT15

Medically necessary when the member is being considered for or is currently undergoing treatment with azathioprine, mercaptopurine, or thioguanine.

Medically necessary when the member is on thiopurine therapy AND has abnormal complete blood count (CBC) results that do not respond to dose reduction.

Investigational for all other indications.

VKORC1 (81355) and warfarin sensitivity multigene panels (81227, 81355, 0030U)

VKORC1 and warfarin sensitivity multigene panels

VKORC1 variant analysis (81355) is medically necessary when the member is being considered for or is currently undergoing treatment with warfarin (e.g., Coumadin, Jantoven).

Warfarin sensitivity multigene panel analysis (e.g., 81227, 81355, 0030U) is medically necessary when the member is being considered for or is undergoing warfarin therapy AND any of the following clinical contexts are present: has not reached a therapeutic dose; is undergoing prophylaxis/treatment of venous thromboembolism; is undergoing prophylaxis/treatment for thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement; OR has a history of myocardial infarction.

Multigene panel analysis to confirm warfarin sensitivity is investigational for all other indications.

UGT1A1 (81350) and UGT2B17 (81479) variant analyses

UGT family

UGT1A1 variant analysis (81350) is medically necessary when the member is being considered for or is currently undergoing treatment with listed drugs including sacituzumab govitecan-hziy (e.g., Trodelvy).

UGT2B17 variant analysis (81479) is medically necessary when the member is being considered for or is currently undergoing treatment with belzutifan (e.g., Welireg).

UGT variant testing is investigational for indications other than those specified above.

Other single-gene variant analyses and large pharmacogenetic panels

Other genes and panels

Variant analysis of other single genes for drug metabolizer status (examples include COMT, CYP1A2, KIF6, OPRM1, TYMS) is considered investigational for drug-metabolizer assessment indications unless specific medical necessity criteria are stated elsewhere in this policy.

Large pharmacogenetic multi-gene panels lack consistent professional society guidance and have mixed evidence of clinical utility; therefore large panels are considered investigational for all indications except where small targeted-panel coverage is explicitly permitted by other criteria in this policy (e.g., specified warfarin panels).

FDA/guideline gene-drug clinical management nodes (excerpt)

Gene-drug pairs with explicit FDA therapeutic management recommendations in this excerpt:

DPYD — For capecitabine and fluorouracil: intermediate or poor DPYD metabolizers are at higher risk of severe, life-threatening, or fatal toxicities; no safe dose has been established for poor metabolizers and data are insufficient to recommend a dose for intermediate metabolizers; withhold or discontinue in the presence of early-onset or unusually severe toxicity.

TPMT/NUDT15 — For azathioprine, mercaptopurine, thioguanine: intermediate or poor metabolizers have altered active metabolite concentrations and higher myelosuppression risk; consider alternative therapy in poor metabolizers and dosage reductions in intermediate metabolizers per FDA labeling and guideline guidance.

VKORC1/CYP2C9 — For warfarin: select initial dosage taking into account VKORC1 (-1639G>A) and CYP2C9 genotypes and monitor/adjust dosages based on INR per FDA recommendations.

CYP3A5 — For tacrolimus: intermediate or normal CYP3A5 metabolizers may have lower tacrolimus concentrations; measure tacrolimus trough whole blood concentrations and adjust dosage accordingly.

Pharmacogenetic panel and single-gene criteria (summary)

The policy includes reformatted and in some cases expanded clinical criteria for coverage of pharmacogenetic tests, notably permitting small targeted warfarin-related panels and adding brand names into VKORC1 and DPYD criteria.

Coverage allowed for small targeted warfarin sensitivity panels when clinical criteria are met; VKORC1 variant (-1639G>A) and CYP2C9 considerations are referenced per FDA Table of Pharmacogenetic Associations and clinical contexts listed in policy (see warfarin panel criteria).

Policy reference table updated to include new PLA/CPT molecular codes (examples: 0476U, 0477U, 0516U, 0423U, 0434U, 0437U, 0438U); these coding updates are operational and illustrative, not a guarantee of coverage.

Clinical criteria for many single-gene tests were reformatted for clarity; where FDA/guideline therapeutic management recommendations exist they are cited and used to define medically necessary indications (e.g., TPMT/NUDT15, DPYD, VKORC1).

Coding, CPT/PLA/Proprietary Codes and Reference Table

Example CPT/proprietary codes referencedmixed

0345U	Example proprietary/test-specific CPT-like code referenced for pharmacogenetic panel
81418	Molecular pathology multigene panel (example listed for some PGx panels)
0173U	Psych HealthPGx panel (example)
0423U	Genomind Pharmacogenetics Report (example)
81225	CYP2C19 (single gene) (example)
81226	CYP2D6 (single gene) (example)
81335	TPMT genotyping (example)

Referenced CPT/PLA codesmixed

81381	HLA-B*57:01 variant analysis
81479	Unlisted molecular pathology procedure / used for certain single-gene variant analyses (e.g., NAT2, UGT2B17, CYP4F2)
81306	TPMT variant analysis
81335	NUDT15 variant analysis
81227	Multigene pharmacogenomic panel (warfarin sensitivity)
0034U	PLA/other TPMT-related pharmacogenetic test code referenced
0169U	PLA/other NUDT15-related pharmacogenetic test code referenced
0030U	Warfarin sensitivity related PLA code referenced

TPMT/NUDT15 testingmixedCovered

81306	TPMT variant analysis
81335	NUDT15 variant analysis
0034U	PLA/other TPMT-related pharmacogenetic test code referenced
0169U	PLA/other NUDT15-related pharmacogenetic test code referenced

DPYD testingmixedCovered

81232

DPYD variant analysis

Warfarin-related genotypingmixedCovered

81227	Multigene warfarin sensitivity panel (warfarin-related genotyping)
81355	VKORC1 variant analysis
0030U	Warfarin sensitivity related PLA code referenced

New/updated molecular CPT/PLA codesCPT

0476U	PLA code added to policy reference table
0477U	PLA code added to policy reference table
0516U	PLA code added to policy reference table
0423U	CPT molecular code added to policy reference table
0434U	CPT molecular code added to policy reference table
0437U	CPT molecular code added to policy reference table
0438U	CPT molecular code added to policy reference table

Coverage guarantee — informational note

Coverage guaranteeNone — codes and tests listed are informational and do not guarantee coverage.

Purpose of listed codesExamples are provided to help navigate claims and criteria, not to be comprehensive.

Reference for complete listProviders should see the Concert Platform for a comprehensive list of registered tests.

Coding guidanceProviders must reference up-to-date professional coding guidance when submitting claims.

Provider and Billing Actions — Authorization, Documentation, and Operational Notes

Billing Rule

Coding guidance and Concert Platform referral

Providers should reference current professional coding guidance when submitting claims. CPT and PLA codes listed in this policy are examples and not exhaustive; inclusion or exclusion does not guarantee coverage. For a comprehensive, up-to-date list of registered tests and applicable codes, see the Concert Platform.

Reference most up-to-date professional coding guidance when submitting claims.
See the Concert Platform for a comprehensive list of registered tests and codes.

Prior Authorization

BCHE single-gene authorization condition

BCHE variant analysis (81479) is medically necessary only when the member is being considered for or is currently receiving mivacurium (e.g., Mivacron) or succinylcholine (e.g., Anectine, Suxamethonium). BCHE testing is investigational for all other indications.

Definitions and Key Terms

Pharmacogenetic tests — definition and methodologies

DefinitionGermline genetic tests developed to aid assessment of an individual’s response to drug treatment or to predict risk of toxicity from a specific drug treatment.

When performedPrior to initiation of treatment to identify variants affecting response or risk, or during treatment to assess adverse reactions or treatment response.

Typical methodologiesGene sequencing, deletion/duplication analysis, and single nucleotide variant testing.

Primary useInform drug selection, dosing, or identify risk of adverse drug reactions.

Pharmacogenetic panel — definition and guidance note

DefinitionA multigene test intended to identify pharmacogenomic variants across many genes.

Policy Summary

PayerCentene

PolicyConcert Genetic Testing: Pharmacogenetics

Policy CodePolicy N/A

Change TypeOperational and coding updatescriteria reformatted

Effective DateN/A

Next Review DateN/A

Key ActionProviders should reference current professional coding guidance and the Concert Platform for the comprehensive list of registered tests.

SourceLink

On This Page

HLA-B*57:01 — For abacavir: do not use abacavir in patients positive for HLA-B*57:01 (testing guides avoidance of abacavir).

HLA-B*15:02 — For carbamazepine, phenytoin/fosphenytoin: avoid use in HLA-B*15:02 positive patients unless benefit outweighs risk due to Steven-Johnson syndrome/TEN risk.

UGT1A1 — For irinotecan, belinostat, sacituzumab govitecan-hziy: poor or intermediate metabolizers may require dose reductions or increased monitoring for neutropenia/other toxicity per labeling.

CYP2D6 — For multiple drugs (e.g., tramadol, codeine, deutetrabenazine, venlafaxine): metabolizer status (poor or ultrarapid) can affect active metabolite concentrations and risks (reduced efficacy or increased toxicity); FDA guidance includes drug-specific recommendations and age-related contraindications for certain genotype–drug combinations.

NAT2 — For amifampridine: poor metabolizers should use the lowest starting dose and monitor; specific dosing guidance for amifampridine phosphate is noted in FDA labeling.

TPMT/NUDT15 (oncology context) — Guidelines (e.g., NCCN) recommend TPMT testing in patients who develop severe neutropenia after starting 6-mercaptopurine in certain leukemia contexts.

Medically necessary: 81479 when considering mivacurium or succinylcholine.
Investigational: 81479 for other indications.

Prior Authorization

CYP2C9 single-gene authorization condition

CYP2C9 variant analysis (81227) is medically necessary when the member is being considered for or is currently undergoing treatment with listed CYP2C9-affected drugs (examples in policy). CYP2C9 testing is investigational for all other indications.

Medically necessary: 81227 when prescribing drugs with CYP2C9 interactions (see policy drug list).
Investigational: 81227 for other indications.

Prior Authorization

CYP2C19 single-gene authorization condition

CYP2C19 variant analysis (81225) is medically necessary when the member is being considered for or is currently undergoing treatment with specified drugs (for example, clopidogrel). CYP2C19 testing is investigational for all other indications.

Medically necessary: 81225 when considering or using clopidogrel and other listed drugs.
Investigational: 81225 for other indications.

Prior Authorization

CYP2D6 single-gene authorization condition

CYP2D6 variant analysis (81226 and related PLA codes) is medically necessary when the member is being considered for or is currently undergoing treatment with drugs listed in the policy (e.g., codeine, tramadol, certain antipsychotics, and others). CYP2D6 testing is investigational for all other indications, including routine tamoxifen management in some settings as noted.

Medically necessary: 81226 (and associated PLA codes) when managing therapy with listed CYP2D6-affected drugs.
Investigational: CYP2D6 testing for other indications, including some tamoxifen uses.

Prior Authorization

CYP3A5 single-gene authorization condition and tacrolimus monitoring

CYP3A5 variant analysis (81231) is medically necessary when the member is being considered for or is currently undergoing treatment with tacrolimus (e.g., Prograf, Envarsus, Astagraf). CYP3A5 testing is investigational for all other indications. Therapeutic drug monitoring of tacrolimus concentrations should guide dose adjustments informed by CYP3A5 metabolizer status.

Medically necessary: 81231 when considering or using tacrolimus.
Investigational: 81231 for other indications.
Operational note: Measure tacrolimus trough whole blood concentrations and adjust dosing based on concentrations and CYP3A5 status.

Prior Authorization

CYP4F2 single-gene authorization condition

CYP4F2 variant analysis (81479) is medically necessary when the member is being considered for or is currently undergoing treatment with warfarin (e.g., Coumadin, Jantoven). CYP4F2 testing is investigational for all other indications. Use genotype (with CYP2C9 and VKORC1 when available) to inform initial warfarin dosing and monitor INR to guide dose adjustments.

Medically necessary: 81479 when considering or using warfarin.
Investigational: 81479 for other indications.
Operational note: Select initial warfarin dose considering CYP4F2, CYP2C9, VKORC1 genotypes and clinical factors; monitor and adjust based on INR.

Prior Authorization

DPYD single-gene authorization condition and treatment action

DPYD variant analysis (81232) is medically necessary when the member is being considered for or is currently undergoing treatment with fluorouracil or capecitabine. In intermediate or poor DPYD metabolizers, there is higher risk of severe or life‑threatening toxicity; withhold or discontinue fluorouracil or capecitabine in the presence of early-onset or unusually severe toxicity.

Medically necessary: 81232 when considering or using fluorouracil or capecitabine.
Clinical action (FDA-based): Withhold or discontinue fluorouracil/capecitabine for intermediate/poor metabolizers or with early/unusually severe toxicity.

Prior Authorization

HLA-A*02:01 single-gene authorization condition

HLA-A*02:01 variant analysis (81379, 81380, 81381) is medically necessary for adults (age ≥18) with unresectable or metastatic uveal melanoma who have not had rapid progression of disease. HLA-A*02:01 testing is investigational for all other indications.

Medically necessary: 81379/81380/81381 for adults with unresectable or metastatic uveal melanoma without rapid progression.
Investigational: HLA-A*02:01 testing for other indications.

Prior Authorization

HLA-B*15:02 single-gene authorization condition

HLA-B*15:02 variant analysis (81381) is medically necessary when the member is being considered for or is currently undergoing treatment with carbamazepine, phenytoin, or fosphenytoin (and other listed anticonvulsants). HLA-B*15:02 testing is investigational for all other indications.

Medically necessary: 81381 when considering carbamazepine, phenytoin, or fosphenytoin.
Investigational: 81381 for other indications.

Prior Authorization

HLA-B*57:01 single-gene authorization condition and prior auth note

HLA-B*57:01 variant analysis (81381) is medically necessary when the member is being considered for or is currently undergoing treatment with abacavir. Prior authorization or medical necessity documentation should reflect the indication for abacavir therapy. HLA-B*57:01 testing is investigational for other indications.

Medically necessary: 81381 when considering abacavir therapy.
Operational note: Prior authorization/medical necessity documentation should indicate abacavir treatment intent.

Prior Authorization

NAT2 single-gene authorization condition

NAT2 variant analysis (81479) is medically necessary when the member is being considered for or is currently undergoing treatment with amifampridine phosphate (e.g., Firdapse, Ruzurgi). NAT2 testing is investigational for all other indications.

Medically necessary: 81479 when considering amifampridine phosphate.
Investigational: 81479 for other indications.

Prior Authorization

TPMT/NUDT15 prior authorization and medical necessity

TPMT and NUDT15 variant analysis (81306, 81335, 0034U, 0169U) is medically necessary when the member is being considered for or is on thiopurine therapy (azathioprine, mercaptopurine, thioguanine), or when on thiopurine therapy with abnormal CBCs not responsive to dose reduction. TPMT/NUDT15 testing is investigational for other indications.

Medically necessary: 81306/81335/0034U/0169U when initiating thiopurine therapy or for abnormal CBCs on thiopurines not responsive to dose reduction.
Investigational: TPMT/NUDT15 testing for other indications.

Denial Risk

Other single-gene tests — investigational

Variant analysis of other single genes for pharmacogenetic purposes (e.g., COMT, CYP1A2, KIF6, OPRM1, TYMS, and other genes listed in policy) is considered investigational for drug metabolizer status unless specifically listed as medically necessary in this policy.

Examples considered investigational: COMT, CYP1A2, KIF6, OPRM1, TYMS and others.
These tests are investigational for pharmacogenetic use unless specifically covered above.

Professional guidanceThe document states there are no professional society guidelines that address clinical utility of large pharmacogenetic panels.

FDA stanceThe FDA does not address the usage of pharmacogenetic panels per the policy text.

Evidence summaryStudies have conflicting results and varying designs; clinical utility is difficult to determine and evidence certainty may be low.

FDA Table of Pharmacogenetic Associations — definition and role

DefinitionAn FDA resource (Table of Pharmacogenetic Associations) listing gene-drug interactions with therapeutic management recommendations.

RoleUsed to inform gene-specific clinical management recommendations cited in the policy (examples include BCHE and others).

ScopeIncludes entries where data support therapeutic management actions for specific gene-drug pairs.

FDA Table of Pharmacogenetic Associations — restated definition

Definition (restated)FDA-maintained table detailing gene-drug interactions for which data support therapeutic management recommendations.

Example useCited in the policy for CYP3A5/tacrolimus management (measure concentrations and adjust dosing).

Policy linkageReferenced across single-gene sections to support management recommendations and coverage considerations.

Poor/intermediate metabolizer — genotype-derived phenotype

DefinitionGenotype-derived phenotypes (poor or intermediate metabolizers) indicate decreased metabolic enzyme activity associated with altered drug concentrations and increased adverse reaction risk.

Clinical implicationIntermediate or poor metabolizer status may require dosage reduction or alternative therapy (example: TPMT/NUDT15 for azathioprine).

Use in policyThe policy uses these phenotype definitions to determine medically necessary testing and management recommendations.

FDA pharmacogenetic guidance — cross-reference to FDA Table

Cross-referencePolicy references the FDA Table of Pharmacogenetic Associations for therapeutic management recommendations (e.g., VKORC1 and CYP2C9 guidance for warfarin dosing).

Practical actionSelect initial warfarin dosage taking into account VKORC1 and CYP2C9 genotypes and monitor/adjust based on INR as per FDA guidance.

Policy usageFDA table entries are cited to support gene-specific coverage and clinical management nodes throughout the policy.