CurrentWellCarePolicy N/A

V1.2024 Concert Genetics Genetic Testing Pharmacogenetics

Defines medical necessity and investigational status for pharmacogenetic panel tests and multiple single-gene variant analyses (e.g., CYP2C9, CYP2C19, CYP2D6, BCHE, DPYD, HLA-B*15:02, HLA-B*57:01, TPMT/NUDT15, UGT1A1, VKORC1, CYP3A5, CYP4F2, NAT2, UGT2B17, other single genes) and lists associated CPT/PLA codes and applicable ICD-10 codes where provided. Provides FDA/NCCN context and references.

Policy Summary

PayerWellCare

PolicyV1.2024 Concert Genetics Genetic Testing Pharmacogenetics

Policy CodePolicy N/A

Change TypeNo material change

Effective Date

Next Review Date

Key ActionProviders must document that testing is for one of the medically necessary drug‑treatment indications listed in the policy to support coverage of single‑gene variant analyses.

SourceLink

POLICY UPDATE CHANGES

No material changes — policy content remains unchanged.

1Panel testing stance: investigational

MultipleSingle-gene tests medically necessary for listed drug indications

ManySingle-gene tests investigational for other indications

Coverage Summary

This policy covers pharmacogenetic genetic testing (panel and single-gene variant analyses). The overall coverage stance is mixed: pharmacogenetic multi-gene panels (listed CPT/PLA codes) are considered investigational for all indications, while numerous single-gene variant analyses are listed as medically necessary for specific drug-treatment indications and investigational for other uses. Panel testing is explicitly identified as investigational, and single-gene tests have multiple, indication-specific medically necessary criteria.

Scope / High-level

SubjectPharmacogenetic genetic testing (panel and single-gene variant analyses)

Coverage stancemixed

StatusCURRENT

Last review2023-11

NotePanel tests: investigational

NoteSingle-gene: covered for specific drug indications

Medical Necessity and Investigational Criteria

Pharmacogenetic Panel Tests

Coverage position for multi-gene pharmacogenetic panels

Use of pharmacogenetic testing panels (codes: 81418, 0029U, 0030U, 0033U, 0173U, 0345U, 0347U, 0348U, 0349U, 0350U, 0380U, 0423U, 0434U, 0437U, 0438U) is considered investigational for all indications

BCHE Variant Analysis (81479)

BCHE variant analysis considered medically necessary when:

ONE of

Member is being considered for or is currently undergoing treatment with mivacurium (e.g., Mivacron)
Member is being considered for or is currently undergoing treatment with succinylcholine (e.g., Anectine, Suxamethonium)

BCHE variant analysis (81479) is investigational for all other indications

CYP2C9 Variant Analysis (81227)

CYP2C9 variant analysis considered medically necessary when member is being considered for or currently undergoing treatment with any of the following drugs:

siponimod (e.g., Mayzent)

celecoxib (e.g., Celebrex, Elyxyb)

dronabinol (e.g., Marinol, Syndros)

erdafitinib (e.g., Balversa)

flurbiprofen (e.g., Ansaid)

fosphenytoin (e.g., Cerebyx, Sesquient)

CYP2C19 Variant Analysis (81225)

CYP2C19 variant analysis considered medically necessary when specific drug/context criteria are met:

For clopidogrel + PCI

Member is being considered for or is currently undergoing treatment with clopidogrel (e.g., Plavix)
Will be undergoing percutaneous coronary intervention (PCI)
Has acute coronary syndromes (ACS)
ONE of
- Is at high risk for poor outcomes (e.g., urgent PCI for an ACS event, elective PCI for unprotected left main disease or last patent coronary artery)

CYP2D6 Variant Analysis (81226, 0070U-0076U)

CYP2D6 variant analysis considered medically necessary when managing treatment with specific drugs:

eliglustat (e.g., Cerdelga)

tetrabenazine (e.g., Xenazine)

amphetamines (e.g., Adzenys, Dyanavel, Evekeo)

aripiprazole (e.g., Abilify, Abilify Maintena)

aripiprazole lauroxil (e.g., Aristada)

atomoxetine (e.g., Strattera)

CYP3A5 Variant Analysis (81231)

CYP3A5 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with tacrolimus (e.g., Protopic, Envarsus, Astagraf, Prograf)

CYP3A5 variant analysis (81231) is investigational for all other indications

CYP4F2 Variant Analysis (81479)

CYP4F2 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with warfarin (e.g., Coumadin, Jantoven)

CYP4F2 variant analysis (81479) is investigational for all other indications

DPYD Variant Analysis (81232)

DPYD variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with fluorouracil (e.g., Adrucil)

Member is being considered for or is currently undergoing treatment with capecitabine (e.g., Xeloda)

DPYD variant analysis (81232) is investigational for all other indications

HLA-B*15:02 Variant Analysis (81381)

HLA-B*15:02 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with any carbamazepine-containing therapy (e.g., Tegretol, Carbatrol, Epitol, Equetro)

Member is being considered for or is currently undergoing treatment with phenytoin (e.g., Dilantin, Phenytek)

Member is being considered for or is currently undergoing treatment with fosphenytoin (e.g., Cerebyx, Sesquient)

HLA-B*15:02 variant analysis (81381) is investigational for all other indications

HLA-B*57:01 Variant Analysis (81381)

HLA-B*57:01 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with abacavir (e.g., Ziagen)

HLA-B*57:01 variant analysis (81381) is investigational for all other indications

NAT2 Variant Analysis (81479)

NAT2 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with amifampridine/amifampridine phosphate (e.g., Firdapse, Ruzurgi)

NAT2 variant analysis (81479) is investigational for all other indications

TPMT and NUDT15 Variant Analysis

TPMT and NUDT15 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with azathioprine (e.g., Imuran, Azasan)

Member is being considered for or is currently undergoing treatment with mercaptopurine (e.g., Purinethol, Purixan)

Member is being considered for or is currently undergoing treatment with thioguanine (e.g., Tabloid)

Member is on thiopurine therapy and has had abnormal complete blood count results that do not respond to dose reduction

TPMT and NUDT15 variant analysis (81306, 81335, 0034U, 0169U) is investigational for all other indications

UGT1A1 Variant Analysis (81350)

UGT1A1 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with irinotecan (e.g., Onivyde, Camptosar)

Member is being considered for or is currently undergoing treatment with belinostat (e.g., Beleodaq)

Member is being considered for or is currently undergoing treatment with sacituzumab govitecan-hziy (e.g., Trodelvy)

UGT1A1 variant analysis (81350) is investigational for all other indications

VKORC1 Variant Analysis (81355)

VKORC1 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with warfarin (e.g., Coumadin, Jantoven)

VKORC1 variant analysis (81355) is investigational for all other indications

UGT2B17 Variant Analysis (81479)

UGT2B17 variant analysis considered medically necessary when:

Member is being considered for or is currently undergoing treatment with belzutifan (e.g., Welireg)

UGT2B17 variant analysis (81479) is investigational for all other indications

Other Single Gene Variant Analyses

Variant analysis of other single genes for drug metabolizer status

Variant analysis of all other genes for drug metabolizer status is considered investigational, including but not limited to: COMT (0032U, 81479), CYP1A2 (0031U, 81479), KIF6 (81479), OPRM1 (81479), SLCO1B1 (81328), TYMS (81479)

Coding

Pharmacogenetic panel CPT/PLA codes (considered investigational)CPTNot Covered

81418	Pharmacogenomic (multi-gene) panel (listed as investigational here)
0029U	PLA / proprietary panel code (listed as investigational)
0030U	PLA / proprietary panel code (listed as investigational)
0033U	PLA / proprietary panel code (listed as investigational)
0173U	PLA / proprietary panel code (listed as investigational)
0345U	PLA / proprietary panel code (listed as investigational)
0347U	PLA / proprietary panel code (listed as investigational)
0348U	PLA / proprietary panel code (listed as investigational)
0349U	PLA / proprietary panel code (listed as investigational)
0350U	PLA / proprietary panel code (listed as investigational)

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Medically necessary single-gene variant CPT codesCPTCovered

81479	Unlisted molecular pathology procedure (used for multiple single gene tests such as BCHE, CYP4F2, NAT2, UGT2B17, COMT, CYP1A2, KIF6, OPRM1, TYMS, etc.)
81227	CYP2C9 variant analysis
81225	CYP2C19 variant analysis
81226	CYP2D6 variant analysis
0070U	CYP2D6 common variants and copy number (Mayo) PLA
0071U	CYP2D6 full gene sequencing PLA
0072U	CYP2D6-2D7 hybrid targeted sequence analysis PLA
0073U	CYP2D7-2D6 hybrid gene analysis PLA
0074U	CYP2D6 nonduplicated gene analysis PLA
0075U	CYP2D6 5' gene duplication/multiplication targeted sequence analysis PLA

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ICD-10 codes referenced in examplesICD-10

F01-F69	Mental, behavioral and neurodevelopmental disorders range referenced
F80-F99	Behavioral and emotional disorders with onset usually in childhood and adolescence
Z81.8	Family history of other mental and behavioral disorders
Z86.59	Personal history of other mental and behavioral disorders
I20.0	Unstable angina
I21.01-I22.9	Acute myocardial infarction range
I24.1	Other forms of acute ischemic heart disease
I25.110	Atherosclerotic heart disease of native coronary artery with unstable angina pectoris
I63.50-I63.549	Cerebral infarction range
I66.01-I66.9	Occlusion and stenosis of cerebral arteries causing cerebral infarction range

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Provider Actions & Billing Impact

Documentation Required

Indication documentation required

Document the clinical indication on the medical record when ordering single-gene pharmacogenetic variant testing. The record should state that testing is being performed for one of the medically necessary drug-treatment indications named in the policy (for example, that the member is being considered for or is currently undergoing treatment with the specific named drug).

Reference the specific drug indication named in the policy (e.g., testing is for management of warfarin dosing, clopidogrel with PCI, azathioprine/mercaptopurine therapy, tacrolimus management, etc.).

Denial Risk

Panel tests not covered

Claims for pharmacogenetic multi-gene panel tests listed in the policy are considered investigational for all indications and are at risk for denial.

81418
0029U
0030U
0033U
0173U
0345U
0347U
0348U
0349U
0350U
0380U
0423U
0434U
0437U
0438U

Background, Evidence, and Definitions

Pharmacogenetic tests are germline genetic tests developed to assess an individual's likely drug response or risk of drug toxicity and may be done prior to or during treatment. Common methodologies include genotyping and single nucleotide variant testing. The policy references the FDA Table of Pharmacogenetic Associations as a source of gene–drug therapeutic management recommendations informing coverage determinations. Examples of panel test platforms and associated CPT/PLA codes are listed in the coding sections of the policy.

Citation	Key point
FDA Table of Pharmacogenetic Associations
Provides therapeutic management recommendations for multiple gene–drug pairs cited in policy (examples include BCHE, CYP2C9, CYP2C19) with dosing/avoidance guidance for affected metabolizer groups

Panel: Genetic test analyzing more than one gene (multi-gene pharmacogenetic panel).

Policy Summary

PayerWellCare

PolicyV1.2024 Concert Genetics Genetic Testing Pharmacogenetics

Policy CodePolicy N/A

Change TypeNo material change

Effective Date

Next Review Date

Key ActionProviders must document that testing is for one of the medically necessary drug‑treatment indications listed in the policy to support coverage of single‑gene variant analyses.

SourceLink

On This Page

meloxicam (e.g., Anjeso, Mobic, Vivlodex, Qmiiz ODT)

nateglinide (e.g., Starlix)

phenytoin (e.g., Dilantin, Phenytek)

piroxicam (e.g., Feldene)

warfarin (e.g., Coumadin, Jantoven)

CYP2C9 variant analysis (81227) is investigational for all other indications

Member is being considered for or is currently undergoing treatment with abrocitinib (e.g., Cibinqo)

Member is being considered for or is currently undergoing treatment with belzutifan (e.g., Welireg)

Member is being considered for or is currently undergoing treatment with brivaracetam (e.g., Briviact, Brivajoy)

Member is being considered for or is currently undergoing treatment with citalopram (e.g., Celexa)

Member is being considered for or is currently undergoing treatment with clobazam (e.g., Onfi)

Member is being considered for or is currently undergoing treatment with flibanserin (e.g., Addyi)

Member is being considered for or is currently undergoing treatment with pantoprazole (e.g., Protonix)

CYP2C19 variant analysis (81225) is investigational for all other indications

brexpiprazole (e.g., Rexulti)

clozapine (e.g., Versacloz, FazaClo, Clozaril)

deutetrabenazine (e.g., Austedo)

gefitinib (e.g., Iressa)

iloperidone (e.g., Fanapt)

lofexidine (e.g., Lucemyra)

meclizine (e.g., Antivert, Bonine, Dramamine, Verticalm, Zentrip)

metoclopramide (e.g., Reglan)

oliceridine (e.g., Olinvyk)

pimozide (e.g., Orap)

pitolisant (e.g., Wakix)

propafenone (e.g., Rythmol)

thioridazine (e.g., Mellaril)

tramadol (e.g., ConZip, Ultram)

valbenazine (e.g., Ingrezza)

venlafaxine (e.g., Effexor)

vortioxetine (e.g., Trintellix, Brintellix)

CYP2D6 variant analysis (codes: 81226, 0070U-0076U) is investigational for all other indications, including for managing tamoxifen therapy

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