Providence Genetic Panel Coverage Update

Coverage Criteria

Non-covered When Clinical Utility Is Not Established

Genetic panel testing is not medically necessary when there is insufficient evidence that the panel has proven clinical utility. Clinical utility must be established for every gene and/or component of the panel.

Clinical utility requirements

A. Testing provides a definitive diagnosis or risk classification and ONE of the following applies
- Other clinical and/or laboratory tests were inconclusive.
- Testing avoids a more invasive diagnostic test, such as a muscle biopsy.
B. Test results will guide clinical management, including predictive, diagnostic, prognostic, or therapeutic decisions.

Not Medically Necessary Genetic Panels

The listed panels are not medically necessary when the evidence does not demonstrate proven clinical utility for all genes or other components of the panel.

Denial logic

Published evidence is insufficient to show that every gene and/or component of the panel provides actionable risk, diagnostic, or prognostic information, or information that impacts medical management.
The available evidence does not demonstrate that use of the panel consistently improves diagnostic rates, health outcomes, or treatment decisions.
The panel is included in this policy because focused review of GeneReviews, ECRI, Hayes, NIH Genetic and Rare Diseases (GARD), and laboratory information identified limited evidence of clinical utility.

General Genetic Testing Requirements

Genetic panel tests must satisfy the following laboratory and validation requirements.

Laboratory and validation requirements

The test is Food and Drug Administration (FDA)-approved and/or is performed in a Clinical Laboratory Improvement Amendments (CLIA)-accredited laboratory.
The laboratory offering the panel has scientifically validated the panel for the indication for which it was developed and is being requested.

This policy does not address whole exome sequencing, whole genome sequencing, genetic tests related to reproductive planning, or prenatal testing.

The list of non-covered panels addressed in this policy is not all-inclusive. Because genetic testing changes rapidly, panel names, genes included within a panel, and coding may change after the last policy update.

Other Medical Policies may apply. Use condition-specific or test-specific policies, when available, to review single-gene or genetic panel tests. For example, genetic panel testing for hereditary colorectal cancer is addressed in the Genetic Testing: Inherited Susceptibility to Colorectal Cancer medical policies.

Refer to the PHP Genetic and Molecular Testing company medical policy for genetic panel testing medical-necessity criteria that are not addressed in more specific medical policies. See the Cross References section for medical policies that may apply to specific hereditary or oncologic conditions.

FDA approval or clearance does not, by itself, establish medical necessity or serve as a basis for coverage. FDA information in this policy is provided for informational purposes only.

Clinical management must not be changed based solely on a variant of uncertain significance (VUS). VUS findings may or may not affect protein function, are more common with broad-panel testing, and generally should not prompt interventions reserved for clearly deleterious mutations.

The policy recognizes that clinical utility remains uncertain for many moderate-penetrance genes and that insufficient evidence or lack of management guidelines may prevent a result from supporting a change in care.

Listed non-covered services include, among others: AlloSure Kidney and related transplant assays; Bridge Urinary Tract Infection; Bladder CARE; CancerTYPE ID and Colvera; CxBladder Detect, Monitor, and Triage; DecisionDx-SCC; DetermaRx; Developmental Eye Disease Panel; EarlyDx MethylScan HCC; EpiSwitch CiRT; GeneticsNow Comprehensive Germline Panel; GenoMind Professional PGx Express; HeartCare; Hemiplegic Migraine Panels; Invitae Comprehensive Neuromuscular Disorders, Neuropathies, Dystonia, and Monogenic Inflammatory Panels; Johns Hopkins Metagenomic Next Generation Sequencing Assay for Infectious Disease; Maternal Fetal Screen T1; MindX Blood Test panels for Longevity, Memory/Alzheimer's, Mood, Pain, Stress, and Suicidality; Mind.Px and Molecular Microscope MMDx heart and kidney tests; mRNA Cancer Detect; Oncotype DX Colon Cancer; Oncuria Detect, Monitor, and Predict; Optic Atrophy Panel; PancraGen; Percepta Genomic Sequencing Classifier; Peripheral Neuropathy Genetics Panel; Praxis Somatic Transcriptome and Transcriptome; PreTransplant Risk Assessment (PTRA); PrismaRA; Prospera Assay; +RNAinsight for CancerNext and ATM; Tissue of Origin; TruDiagnostic tests; Tuteva; UriFind Blood Cancer Assay; Versiti congenital Neutropenia Panel; and Vita Risk.

Applicable listed codes include 0012M, 0013M, 0055U, 0087U, 0088U, 0134U, 0136U, 0175U, 0205U, 0258U, 0266U, 0271U, 0288U, 0289U, 0290U, 0291U, 0292U, 0293U, 0294U, 0296U, 0315U, 0319U, 0320U, 0321U, 0323U, 0332U, 0363U, 0365U-0367U, 0420U, 0423U, 0437U, 0456U, 0465U, 0474U, 0493U, 0549U, 0565U, 0616U-0627U, 81479, 81504, 81525, 81540, 81599, 84999, S3844, and S3870. Code descriptions and test names may change.

All unlisted codes are reviewed for medical necessity, correct coding, and pricing at the claim level. If an unlisted code is submitted for a non-covered service addressed in this policy, it will be denied as not covered. If an unlisted code is submitted for a potentially covered service addressed in this policy, prior authorization is recommended to avoid post-service denial.

Clinical utility must be established for every gene and/or component of a panel. A panel is not supported merely because one or more components have established utility; the complete panel must satisfy the clinical-utility requirements.

AlloSure Kidney; AlloSure Kidney Bridge Urinary Tract Infection; Bladder CARE; CancerTYPE ID; CancerTYPE ID Colvera; CxBladder Detect; CxBladder Monitor; CxBladder Triage; DecisionDx-SCC; DetermaRx; Developmental Eye Disease Panel; EarlyDx MethylScan HCC; EpiSwitch CiRT; GeneticsNow Comprehensive Germline Panel; GenoMind Professional PGx Express, including the CORE Anxiety & Depression Report and/or FULL Mental Health Report; HeartCare; Hemiplegic Migraine Panels; Invitae Comprehensive Neuromuscular Disorders Panel; Invitae Comprehensive Neuropathies Panel; Invitae Dystonia Comprehensive Panel; Invitae Monogenic Inflammatory Panel; Johns Hopkins Metagenomic Next Generation Sequencing Assay for Infectious Disease; Maternal Fetal Screen T1; MindX Blood Test—Longevity, Memory/Alzheimer's, Mood, Pain, Stress, and Suicidality; Mind.Px; Molecular Microscope MMDx Heart Test; Molecular Microscope MMDx Kidney Test; mRNA Cancer Detect; Oncotype DX Colon Cancer; Oncuria Detect, Monitor, and Predict; Optic Atrophy Panel; PancraGen; Percepta Genomic Sequencing Classifier; Peripheral Neuropathy Genetics Panel; Praxis Somatic Transcriptome; Praxis Transcriptome; PreTransplant Risk Assessment (PTRA); PrismaRA; Prospera Assay; +RNAinsight for CancerNext; +RNAinsight for ATM; Tissue of Origin; TruDiagnostic tests; Tuteva; UriFind Blood Cancer Assay; Versiti congenital Neutropenia Panel; and Vita Risk.

Genetic panels may range from three genes to thousands of genes and can provide information of unclear clinical significance or information that would not change management. Such findings may lead to unnecessary interventions and anxiety.

High-quality peer-reviewed studies have shown value for only certain panels in diagnosis, risk assessment, or treatment. The panels listed in this policy lack sufficient evidence that all genes or components consistently provide actionable information or improve health outcomes.

The code list is provided as a courtesy and may not be all-inclusive. Inclusion or omission of a code neither implies nor guarantees reimbursement or coverage. Some codes may not require routine medical-necessity review but remain subject to provider contracts, member benefits, eligibility, and potential utilization audit.

HCPCS and CPT codes may be subject to National Correct Coding Initiative procedure-to-procedure bundling edits and daily maximum edits, also known as medically unlikely edits (MUEs), published by the Centers for Medicare and Medicaid Services. This policy does not take precedence over NCCI edits or MUEs; refer to CMS coding guidelines and applicable code combinations.

Non-Covered Codes

Non-covered named tests and panelsCPTNot Covered

0321U	Detection and Resistance Test Bladder CARE
0549U	EarlyDx MethylScan HCC
0012M	CxBladder Detect
0013M	CxBladder Monitor
0363U	CxBladder Triage
0315U	DecisionDx-SCC
0288U	DetermaRx
0565U	EarlyDx MethylScan HCC
0332U	EpiSwitch CiRT (Checkpoint-inhibitor Response Test)
0474U	Genomind Professional PGx Express

1–10 of 12

1/2

Non-covered molecular and genomic testsCPTNot Covered

0294U	MindX Blood Test—Longevity
0289U	MindX Blood Test—Memory/Alzheimer's
0291U	MindX Blood Test—Mood
0290U	MindX Blood Test—Pain
0292U	MindX Blood Test—Stress
0293U	MindX Blood Test—Suicidality
0258U	Mind.Px Molecular Microscope MMDx
0087U	Molecular Microscope MMDx Heart Test
0088U	Molecular Microscope MMDx Kidney Test
0296U	mRNA Cancer Detect

1–10 of 15

1/2

Non-covered named tests and panelsCPTNot Covered

0319U	PreTransplant Risk Assessment (PTRA)
0456U	PrismaRA
0493U	Prospera Assay
0134U	+RNAinsight for CancerNext
0136U	+RNAinsight for ATM
0616U	TruDiagnostic tests
0617U	TruDiagnostic tests
0618U	TruDiagnostic tests
0619U	TruDiagnostic tests
0620U	TruDiagnostic tests

1–10 of 20

1/2

Not Covered Genetic Panel and Molecular Test CodesCPTNot Covered

0012M	Oncology (urothelial), mRNA, gene expression profiling by real-time quantitative PCR of five genes (MDK, HOXA13, CDC2 [CDK1], IGFBP5, and XCR2), utilizing urine, algorithm reported as a risk score for having urothelial carcinoma
0013M	Oncology (urothelial), mRNA, gene expression profiling by real-time quantitative PCR of five genes (MDK, HOXA13, CDC2 [CDK1], IGFBP5, and CXCR2), utilizing urine, algorithm reported as a risk score for having recurrent urothelial carcinoma
0087U	Cardiology (heart transplant), mRNA gene expression profiling by microarray of 1283 genes, transplant biopsy tissue, allograft rejection and injury algorithm reported as a probability score
0088U	Transplantation medicine (kidney allograft rejection), microarray gene expression profiling of 1494 genes, utilizing transplant biopsy tissue, algorithm reported as a probability score for rejection
0134U	Hereditary pan cancer (eg, hereditary breast and ovarian cancer, hereditary endometrial cancer, hereditary colorectal cancer), targeted mRNA sequence analysis panel (18 genes)
0136U	ATM (ataxia telangiectasia mutated) (eg, ataxia telangiectasia) mRNA sequence analysis
0175U	Psychiatry (eg, depression, anxiety), genomic analysis panel, variant analysis of 15 genes
0205U	Ophthalmology (age-related macular degeneration), analysis of 3 gene variants (2 CFH gene, 1 ARMS2 gene), using PCR and MALDI-TOF, buccal swab, reported as positive or negative for neovascular age-related macular-degeneration risk associated with zinc supplements
0258U	Autoimmune (psoriasis), mRNA, next-generation sequencing, gene expression profiling of 50-100 genes, skin-surface collection using adhesive patch, algorithm
0271U	Hematology (congenital neutropenia), genomic sequence analysis of 24 genes, blood, buccal swab, or amniotic fluid

1–10 of 33

1/4

Non-covered molecular and genomic assaysCPTNot Covered

0420U	Oncology (urothelial), mRNA expression profiling by real-time quantitative PCR of MDK, HOXA13, CDC2, IGFBP5, and CXCR2 in combination with droplet digital PCR (ddPCR) analysis of 6 single-nucleotide polymorphisms (SNPs) genes TERT and FGFR3, urine, algorithm reported as a risk score for urothelial carcinoma
0423U	Psychiatry (eg, depression, anxiety), genomic analysis panel, including variant analysis of 26 genes, buccal swab, report including metabolizer status and risk of drug toxicity by condition
0437U	Psychiatry (anxiety disorders), mRNA, gene expression profiling by RNA sequencing of 15 biomarkers, whole blood, algorithm reported as predictive risk score
0465U	Oncology (urothelial carcinoma), DNA, quantitative methylation-specific PCR of 2 genes (ONECUT2, VIM), algorithmic analysis reported as positive or negative
0474U	Oncology (urothelial), DNA, quantitative methylated real-time PCR of TRNA-Cys, SIM2, and NKX1-1, using urine, diagnostic algorithm reported as a probability index for bladder cancer

Non-covered methylation, expression, and risk-score assaysCPTNot Covered

0588U	Infectious disease (bacterial or viral), 32 genes (29 informative and 3 housekeeping), immune response mRNA, gene expression profiling by split-well whole blood, reported as continuous risk scores for likelihood of bacterial and viral infection and likelihood of severe illness within the next 7 days
0616U	Neurology (dementia), DNA methylation analysis of more than 30,000 sites, whole blood, algorithm reported as positive or negative risk
0617U	Cardiovascular (atherosclerotic cardiovascular disease [ASCVD]), DNA methylation analysis of more than 20,000 sites, whole blood, algorithm reported as positive or negative risk
0618U	Psychiatry (bipolar disorder), DNA methylation analysis of more than 10,000 sites, whole blood, algorithm reported as positive or negative risk
0619U	Pulmonary (chronic obstructive pulmonary disease [COPD]), DNA methylation analysis of more than 18,000 sites, whole blood, algorithm reported as positive or negative risk
0621U	Oncology (hepatocellular carcinoma), DNA methylation analysis of more than 5,000 sites, whole blood, algorithm reported as positive or negative risk
0621U	Infectious disease (Lyme borreliosis), DNA methylation analysis of more than 10,000 sites, whole blood, algorithm reported as positive or negative risk
0622U	Psychiatry (major depressive disorder), DNA methylation analysis of more than 20,000 sites, whole blood, algorithm reported as positive or negative risk
0623U	Autoimmune (multiple sclerosis), DNA methylation analysis of more than 5,000 sites, whole blood, algorithm reported as positive or negative risk
0624U	Hepatology (nonalcoholic steatohepatitis [NASH]), DNA methylation analysis of 5,000 sites, whole blood, algorithm reported as positive or negative risk

1–10 of 17

1/2

Non-covered cytogenomic and molecular pathology proceduresCPTNot Covered

81195	Cytogenomic (genome-wide) analysis, hematologic malignancy, structural variants and copy number variants, optical genome mapping (OGM)
81228	Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number variants
81229	Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number and single nucleotide polymorphism variants, comparative genomic hybridization [CGH]
81301	Microsatellite instability analysis (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) of markers for mismatch repair deficiency (e.g., BAT25, BAT26), includes comparison of neoplastic and normal tissue, if performed
81320	PLCG2 (phospholipase C gamma 2) (eg, chronic lymphocytic leukemia) gene analysis, common variants (eg, R665W, S707F, L845F)
81400	Molecular pathology procedure, Level 1 (e.g., identification of single germline variant [e.g., SNP] by techniques such as restriction enzyme digestion or melt curve analysis)
81401	Molecular pathology procedure, Level 2 (e.g., 2-10 SNPs, 1 methylated variant, or 1 somatic variant [typically using nonsequencing target variant analysis], or detection of a dynamic mutation disorder/triplet repeat)
81402	Molecular pathology procedure, level 3 (e.g., >10 SNPs, 2-10 methylated variants, or 2-10 somatic variants [typically using non-sequencing target variant analysis], immunoglobulin and T-cell receptor gene rearrangements, duplication/deletion)
81403	Molecular pathology procedure, level 4 (e.g. analysis of single exon by DNA sequence analysis, analysis of >10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons)
81404	Molecular pathology procedure, level 5 (e.g., analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by southern blot analysis)

1–10 of 14

1/2

Non-covered hereditary disease, exome, and genomic sequence-analysis panelsCPTNot Covered

81412	Ashkenazi Jewish associated disorders (eg, Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Tay-Sachs disease), genomic sequence analysis panel, must include sequencing of at least 9 genes, including ASPA, BLM, CFTR, FANCC, GBA, HEXA, IKBKAP, MCOLN1, and SMPD1
81413	Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); genomic sequence analysis panel, must include sequencing of at least 10 genes, including ANK2, CASQ2, CAV3, KCNE1, KCNE2, KCNH2, KCNJ2, KCNQ1, RYR2, and SCN5A
81414	Cardiac ion channelopathies (eg, Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia); duplication/deletion gene analysis panel, must include analysis of at least 2 genes, including KCNH2 and KCNQ1
81415	Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis
81416	Exome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis, each comparator exome (eg, parents, siblings) (List separately in addition to code for primary procedure)
81416	Exome (eg, unexplained constitutional or heritable disorder or syndrome); re-evaluation of previously obtained exome sequence (eg, updated knowledge or unrelated condition/syndrome)
81437	Hereditary neuroendocrine tumor related disorders (eg, medullary thyroid carcinoma, parathyroid carcinoma, malignant pheochromocytoma or paraganglioma); genomic sequence analysis panel, 5 or more genes, interrogation for sequence variants and copy number variants
81439	Hereditary cardiomyopathy (eg, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy), genomic sequence analysis panel, must include sequencing of at least 5 cardiomyopathy-related genes (eg, DSG2, MYBPC3, MYH7, PKP2, TTN)
81442	Noonan spectrum disorders (eg, Noonan syndrome, cardio-facio-cutaneous syndrome, Costello syndrome, LEOPARD syndrome, Noonan-like syndrome), genomic sequence analysis panel, must include sequencing of at least 12 genes, including BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, and SOS1
81443	Genetic testing for severe inherited conditions (eg, cystic fibrosis, Ashkenazi Jewish-associated disorders, beta hemoglobinopathies, phenylketonuria, galactosemia), genomic sequence analysis panel, must include sequencing of at least 15 genes

1–10 of 12

1/2

Non-covered oncology, unlisted, and CGH genetic assaysCPT | HCPCSNot Covered

81504	Oncology (tissue of origin), microarray gene expression profiling of >2000 genes, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as tissue
81525	Oncology (colon), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (7 content and 5 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a recurrence score
81540	Oncology (tumor of unknown origin), mRNA, gene expression profiling by real-time RT-PCR of 92 genes (87 content and 5 housekeeping) to classify tumor into main cancer type and subtype, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a probability of a predicted main cancer type and subtype
81599	Unlisted multianalyte assay with algorithmic analysis
84999	Unlisted chemistry procedure
S3844	DNA analysis of the connexin 26 gene (GJB2) for susceptibility to congenital, profound deafness
S3870	Comparative genomic hybridization (CGH) microarray testing for developmental delay, autism spectrum disorder and/or intellectual disability

Provider Actions and Review Requirements

Documentation Required

Submit Clinical Utility Documentation

Submit documentation supporting the clinical utility of the genetic test at the time of the request.

Provide the panel name or the names of the genes and/or components.
Include the laboratory performing or planning to perform the test.
Explain the suspected condition, relevant signs, symptoms, test results, family history when applicable, and how results will affect clinical decision-making.

Documentation Required

Provide Clinical Utility Information

Submit sufficient clinical utility information for the requested genetic panel or test components so medical necessity can be evaluated.

Identify the panel or gene/component names.
Identify the laboratory.
Provide the clinical rationale and supporting documentation, including the expected effect on clinical management.

Policy Background

Genetic panel testing is evaluated component by component for clinical utility, whether the panel contains only a few genes or thousands. Coverage requires that each gene or component support a definitive diagnosis or risk classification, address inconclusive testing or avoid a more invasive diagnostic procedure, and produce results that guide clinical management. Panels without evidence of actionable clinical benefit or improved health outcomes are considered not medically necessary.

Key Definitions

Genetic panel testing

What it evaluatesMultiple genes or genetic test components together.

Testing approachAllows simultaneous testing of multiple genes and/or mutations.

Coverage evaluationClinical utility must be established for each gene or component of the panel.

Clinical utility

Diagnostic or risk resultTesting must allow a definitive diagnosis or risk classification.

Supporting pathwayOther clinical or laboratory tests must have been inconclusive, or the testing must avoid a more invasive diagnostic test, such as a muscle biopsy.

Management impact

Eligibility Requirements

When family history is relevant to the rationale for genetic testing, document the applicable personal and family history in the clinical record. For cancer susceptibility testing, select genes with established clinical utility based on the patient's personal and/or family history of cancer.

For the clinical utility pathway, other clinical and/or laboratory testing should be inconclusive unless the genetic test avoids a more invasive diagnostic procedure, such as a muscle biopsy.

Not Covered Services

Genetic panel tests for which clinical utility has not been established are not covered as medically necessary under this policy. This includes the named tests and panels listed in the policy and panels for which evidence does not show that every gene or component provides actionable risk, diagnostic or prognostic information, affects medical management, or improves health outcomes.

Non-Covered Genetic Panel Tests

Sign up for Providence Health Plan Policy 213 alerts