Genetic Testing
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Aetna's clinical policy bulletin governing when genetic and molecular tests are considered medically necessary, investigational, or not covered for members; applies to providers ordering genetic testing covered by Aetna.
No material clinical or coverage changes in this revision.
Coverage Criteria and Condition-Specific Indications
Inherited Thrombophilias
Aetna considers genetic testing for inherited thrombophilias medically necessary when specific clinical indications or testing strategies are met; routine population screening is not recommended.
ALL of the following
- Factor V Leiden genetic testing is medically necessary for members with an abnormal activated protein C (APC) resistance assay result and any of the following: asymptomatic female planning pregnancy or currently pregnant not taking anticoagulation with additional risk factors; first-degree relative with high-risk thrombophilia; first-degree relative with VTE before age 50; first unprovoked VTE at any age (especially <50); individual with a first VTE and a first-degree relative with VTE before age 50; recurrent VTE; venous thrombosis at unusual sites (eg, cerebral, mesenteric, portal, hepatic veins); VTE associated with oral contraceptives or hormone replacement therapy; VTE during pregnancy or puerperium.
- Testing for prothrombin G20210A (F2) and consideration of combined testing (eg, F5 and F2) is appropriate when results will affect management, and when overlapping phenotypes or potentiation of risk is suspected.
- Testing is medically necessary in relatives of individuals with documented pathogenic thrombophilia variants for the purpose of cascade/variant-specific testing when a causative familial mutation has been identified.
- The American College of Medical Genetics (ACMG) does not recommend random population screening for Factor V Leiden; targeted testing prior to oral contraceptive use may be appropriate for women with personal or family history of venous thrombosis.
Interstitial Lung Disease (ILD)
Aetna considers genetic testing of SP-C (SFTPC) and ABCA3 mutations medically necessary in specific pediatric presentations of interstitial lung disease (ILD) where results will inform diagnosis and management.
ANY of the following
- Infants presenting with acute respiratory failure in the absence of other explanations where surfactant dysfunction is suspected; genetic testing may obviate the need for lung biopsy.
- Older children with chronic ILD presentation or a family history of ILD, especially when diagnostic imaging (radiographic patterns) or bronchoscopic findings are consistent with ILD.
- Testing is indicated when identification of SP-C or ABCA3 mutations would alter management, guide prognosis, or inform family counseling.
Hypophosphatasia
Aetna considers genetic testing for pathogenic variants in ALPL medically necessary to confirm the diagnosis of hypophosphatasia when clinical and biochemical findings support the diagnosis.
ALL of the following
- Clinical features and biochemical testing (low serum and bone alkaline phosphatase activity) suggest hypophosphatasia.
- Molecular testing for bi-allelic pathogenic variants (or a heterozygous pathogenic variant, depending on clinical context) in ALPL is performed to confirm the diagnosis (prenatal context excepted where genetic diagnosis is essential).
Malignant Hyperthermia (MH) and Related Disorders
Aetna considers genetic testing for malignant hyperthermia susceptibility (MHS) medically necessary in the following circumstances and considers genetic testing otherwise investigational.
ANY of the following
- Persons with a positive or equivocal contracture test (eg, CHCT/IVCT) to determine the presence of a specific RYR1 variant considered causative for MH by the European Malignant Hyperthermia Group (EMHG) to enable predictive testing in relatives.
- At-risk relatives of persons with clinically confirmed MHS when a known familial RYR1 variant (considered causative by EMHG) has been identified — mutation-specific testing for cascade predictive purposes.
- Patients with a clinical history suspicious for MH (eg, acute MH episode, masseter muscle rigidity, postoperative myoglobinuria, heat- or exercise-induced rhabdomyolysis) who are unable or unwilling to undergo contracture testing.
Genetic Testing for Mitochondrial Disorders
Aetna considers molecular genetic testing for suspected mitochondrial disorders medically necessary when testing strategy and specimen selection are appropriate to the clinical presentation.
ALL of the following
- Clinical features suggestive of a mitochondrial disorder (eg, multisystem involvement such as ataxia, cardiomyopathy, optic neuropathy, exercise intolerance, lactic acidosis, seizures) or syndromic presentations (eg, MELAS, MERRF, Kearns-Sayre, LHON) where a genetic etiology is likely.
- Testing strategy tailored to the suspected etiology: targeted testing of nuclear genes when a nuclear inheritance pattern is suspected, sequencing of the mitochondrial genome (mtDNA) and/or targeted mtDNA mutation analysis when maternal inheritance or known mtDNA variants are suspected; for many mtDNA variants, testing of muscle tissue may be required because blood testing can be falsely negative.
- Use of multi-gene panels or genomic testing (eg, whole-exome sequencing, whole mitochondrial genome sequencing) is appropriate when single-gene testing or panels are non-diagnostic and a genetic diagnosis would impact management, prognosis, or reproductive counseling.
Genetic Testing for Familial Malignant Melanoma (CDKN2A)
Aetna considers CDKN2A (familial melanoma) genetic testing limited and generally not recommended outside research or very specific contexts because test results rarely alter management; testing may be considered when results would change clinical care or in the context of research/clinical trials.
ANY of the following
- Testing may be considered in families with multiple affected first-degree relatives spanning generations or a high pre-test probability of a CDKN2A pathogenic variant when results would alter clinical management (eg, influence screening recommendations beyond standard dermatologic surveillance) or for enrollment in clinical trials.
- Aetna considers routine CDKN2A testing for familial malignant melanoma not appropriate outside research settings given limited impact on patient management and uncertain clinical utility.
Maturity-Onset Diabetes of the Young (MODY)
Aetna considers genetic testing for MODY (GCK, HNF1A, HNF4A) medically necessary when identification of the genetic subtype will affect treatment or management decisions.
ALL of the following
- Person has hyperglycemia or non–insulin-dependent diabetes with a family history of abnormal glucose metabolism in at least 2 consecutive generations, and the individual or one or more family members were diagnosed before age 25.
- Identification of a pathogenic variant would influence management (eg, choice of oral agents such as sulfonylureas for HNF1A/HNF4A, or conservative/no pharmacologic therapy for GCK-related MODY).
Menkes Disease
Aetna considers genetic testing for Menkes disease medically necessary for children with biochemical evidence consistent with Menkes disease.
ALL of the following
- Child has low serum copper and low serum ceruloplasmin concentrations consistent with Menkes disease.
- Molecular genetic testing (ATP7A sequence analysis and, if indicated, deletion/duplication analysis) is performed to confirm the diagnosis and guide management and genetic counseling.
May-Hegglin Anomaly and Related Disorders (MYH9)
Aetna considers genetic testing for MYH9-associated disorders (eg, May-Hegglin anomaly) limited and appropriate when clinical presentation suggests an inherited giant platelet disorder or a MYH9-related phenotype.
ANY of the following
- Genetic testing may be considered when clinical features (giant platelets, thrombocytopenia, Dohle-like cytoplasmic inclusions, family history, renal disease, sensorineural hearing loss) suggest a MYH9-associated disorder and results would affect diagnosis or reproductive counseling.
- Genetic testing is not recommended for general population screening or routine evaluation of thrombocytopenia without features suggestive of a hereditary platelet disorder.
Initial and Salvage (Genomic) Testing
Initial genomic testing (eg, whole exome sequencing) and salvage strategies (eg, reflex RNA testing, mRNA analysis) are considered medically necessary when they meet condition-specific criteria and when results are expected to impact management, clarify uncertain DNA findings, or avoid invasive procedures.
ANY of the following
- Initial genomic testing (WES/GS) is considered medically necessary when condition-specific WES/GS criteria are met (see Whole Exome Sequencing criteria): genetic etiology likely, evaluation by a board-certified geneticist, counseling provided, alternate etiologies considered, and WES is more efficient than sequential testing.
- Salvage testing strategies (including targeted mRNA/RNA analysis or repeat sequencing/re-analysis of prior genomic data) are considered medically necessary when prior DNA testing yielded variants of uncertain significance that affect splicing or when additional testing (eg, RNA analysis) is likely to resolve classification or would change management.
- Concurrent or reflex mRNA (RNA) sequence analysis alongside DNA testing may be appropriate in hereditary cancer and other genes where predicted splicing variants are detected and where RNA testing can clarify variant impact and change clinical management.
RNA (mRNA) Sequence Analysis — Indications
Aetna considers RNA (mRNA) sequence analysis (RGT) alongside DNA genetic testing appropriate when results will resolve variants of uncertain significance affecting splicing or will otherwise change clinical management.
ANY of the following
- RNA testing is considered medically necessary when DNA testing identifies a variant predicted to affect splicing or when a VUS is suspected to alter mRNA splicing and RNA analysis is likely to clarify classification and affect patient management (eg, hereditary cancer genes, selected diagnostic panels).
- RNA testing may be offered to re-classify inconclusive variants from prior DNA genetic testing when reclassification would change clinical recommendations for the patient or family (eg, surveillance, risk-reduction surgery, targeted therapies, reproductive decision-making).
- Routine use of RNA testing in the absence of a specific indication (eg, no splice-predictive variant or clinical utility) is not recommended.
Applicable Procedure and Diagnosis Codes
| 0214U | Whole exome and mitochondrial DNA sequence analysis, rare diseases, proband |
| 0215U | Whole exome and mitochondrial DNA sequence analysis, rare diseases, proband (alternate) |
| 0218U | DMD gene sequence analysis (muscular dystrophy) |
| 0231U | CACNA1A full gene analysis (eg, spinocerebellar ataxia) |
| 0233U | FXN gene analysis (Friedreich ataxia) |
| 0234U | MECP2 full gene analysis (Rett syndrome) |
| 0235U | PTEN full gene analysis (Cowden syndrome) |
| 0236U | SMN1 and SMN2 full gene analysis (spinal muscular atrophy) |
| 0237U | Cardiac ion channelopathies genomic sequence panel |
| 0238U | Oncology (Lynch syndrome) genomic DNA sequence analysis (MLH1, MSH2, MSH6, PMS2, EPCAM) |
| 81161 | DMD deletion and duplication analysis, if performed |
| 81177 | ATN1 gene analysis — expanded allele detection |
| 81178 | ATXN1 gene analysis — expanded allele detection |
| 81179 | ATXN2 gene analysis — expanded allele detection |
| 81180 | ATXN3 gene analysis — expanded allele detection |
| 81181 | ATXN7 gene analysis — expanded allele detection |
| 81182 | ATXN8OS gene analysis — expanded allele detection |
| 81183 | ATXN10 gene analysis — expanded allele detection |
| 81184 | CACNA1A expanded allele analysis (repeat disorders) |
| 81185 | CACNA1A full gene sequence |
| C16.0-C16.9 | Malignant neoplasm of stomach (with 2 HNPCC-related cancers) |
| C18.0-C21.8 | Malignant neoplasm of colon (HNPCC) |
| D57.00-D57.819 | Sickle cell disorders |
| E83.110 | Hereditary hemochromatosis |
| E84.0-E84.9 | Cystic fibrosis (CFTR) |
| F70-F79 | Intellectual disabilities |
| G10 | Huntington's disease |
| G11.1 | Early-onset cerebellar ataxia (Friedreich's ataxia) |
| I42.0 | Dilated cardiomyopathy (hereditary) |
| I25.110-I25.119 | Atherosclerotic heart disease of native coronary artery with angina pectoris (premature CHD) |
| E83.110 | Hereditary hemochromatosis (covered when criteria met) |
| I42.0 | Dilated cardiomyopathy (hereditary) — supports cardiomyopathy genetic testing (eg 81439) |
| 0214U | Whole exome and mitochondrial DNA sequence analysis, proband |
| 0265U | Whole genome and mitochondrial DNA sequence analysis, multiple specimen types |
| 0426U | Ultra-rapid genome sequence analysis (covered when indicated) |
| 81412 | Ashkenazi Jewish associated disorders genomic sequence analysis panel (>=9 genes) |
| 81413 | Cardiac ion channelopathies genomic sequence analysis panel (>=10 genes) |
| 81434 | Hereditary retinal disorders genomic sequence analysis panel (>=15 genes) |
| 81439 | Hereditary cardiomyopathy genomic sequence analysis panel (>=5 genes) |
| 81441 | Inherited bone marrow failure syndromes sequence analysis panel (>=30 genes) |
| 81448 | Hereditary peripheral neuropathies genomic sequence analysis panel |
| 81460 | Whole mitochondrial genome sequence (heteroplasmy detection) |
| 81425 | Genome (sequence analysis) |
| 81435 | Coloseq hereditary colon cancer panel — Not covered for Coloseq |
| 81436 | Coloseq duplication/deletion analysis panel — Not covered for Coloseq |
| 88381 | Microdissection manual — Not covered for Coloseq |
| 81216 | BRCA2 full sequence — Not covered for Panexia |
| 81217 | BRCA2 known familial variant — Not covered for Panexia |
| 81406 | Molecular pathology procedure Level 7 — Not covered for Panexia |
| 81441 | IBMFS panel — must include sequencing of at least 30 genes |
| 0276U | Inherited thrombocytopenia panel — genomic sequence analysis of 23 genes |
| 0268U | aHUS genetic evaluation panel — genomic sequence analysis of 15 genes |
| 81413 | Cardiac ion channelopathies panel — must include sequencing of at least 10 genes |
| 81412 | Ashkenazi Jewish associated disorders panel — must include sequencing of at least 9 genes |
Prior Authorization, Documentation, and Ordering Guidance
Obtain prior authorization when medical necessity criteria are met
Prior authorization or coverage review is expected; testing must meet the policy's medical necessity criteria (member displays clinical features or is at direct risk, result will directly impact treatment, history/physical/pedigree/counseling/diagnostics performed, and disease‑specific criteria met).
Expect PA for multigene panel testing
Prior authorization may be required when ordering multigene/genomic panels — the request must demonstrate the panel is indicated under the policy (e.g., IBMFS, TAAD, hereditary cancer) and meets the specified clinical criteria.
Ensure selection criteria documented for covered codes
Coverage for many CPT/HCPCS-listed tests is conditional — submit documentation that the member meets the policy's selection/medical‑necessity criteria when seeking coverage for the listed codes.
Verify panel gene content and obtain PA
Genomic sequence analysis panels are defined by minimum gene content; prior authorization is likely required to verify the panel includes the required genes and that the indication matches the policy.
- Confirm panel meets the CPT-specified minimum gene list (e.g., 81413 requires ≥10 genes).
Obtain PA for whole exome and select high‑level panels
Certain high-level genomic procedures (e.g., whole exome sequencing 81415-81417 and cardiac ion channelopathy panels 0237U/81413/81414) are covered only if selection criteria are met — prior authorization or explicit justification will be expected.
- Provide clinical rationale that selection criteria for WES or cardiac panel are satisfied.
PA often required for large multi‑gene commercial panels
Prior authorization may be expected for large commercial multi‑gene panels (e.g., BreastNext, CancerNext) because clinical utility varies; documentation should justify why a broad panel is required versus targeted testing.
- Explain why single‑gene or smaller panel testing is insufficient.
- Provide prior testing results and clinical indications.
Document justification for hereditary colorectal cancer panels
For comprehensive hereditary colorectal cancer panels (ColoNext, ColoSeq), include documentation of personal/family history that meets the policy indications and justify panel testing (sequencing plus deletion/duplication analysis) in the PA request.
- Document relevant personal/family cancer history per policy.
- State why panel testing (versus targeted testing) is needed.
Provide prior CF screening results; justify panel or repeat testing
For cystic fibrosis carrier screening, document prior screening results; ACOG guidance discourages repeat routine screening — extended CFTR sequencing is appropriate only in specific circumstances and may require justification.
- If prior CF screening exists, include results; do not repeat without reason.
- If sweat chloride intermediate or persistent suspicion, document rationale for full CFTR sequencing.
Show clinical utility — diagnosis/prognosis/treatment/reproductive need
Document that testing is expected to confirm diagnosis, inform prognosis, treatment selection, or reproductive management; prior authorization reviewers will expect evidence of expected clinical utility.
- State how results will change management, surveillance, therapy, or reproductive plans.
PA likely or denial risk for investigational hearing‑loss panels
Panels described as investigational/experimental for nonsyndromic hearing loss (e.g., OtoSCOPE, OtoGenome, OtoSeq) may not meet medical necessity and could require prior authorization or be denied.
- If ordering such panels, include evidence supporting clinical utility for the indication.
Test the index case first before cascade/predictive testing
Order molecular testing in the affected/index case before ordering predictive/cascade testing of relatives; predictive testing is informative only when a pathogenic/likely pathogenic familial variant has been identified.
- If no pathogenic familial variant is established, do not proceed with predictive testing of relatives.
Follow gene‑tier testing and require proband variant for HCM cascade testing
For hypertrophic cardiomyopathy (HCM), initial genetic testing should target a tier of genes with strong evidence (e.g., MYH7, MYBPC3, TNNI3, TPM1, MYL2, MYL3, ACTC1, TNNT2) and cascade testing of relatives is appropriate only after a pathogenic/likely pathogenic variant is identified in the proband.
- Include proband clinical diagnosis and family history in PA and documentation.
- Do not offer predictive testing to relatives when only a VUS is present.
Document high‑probability LQTS criteria and family findings before testing
Genetic testing is recommended for index patients with high‑probability Long QT Syndrome (Schwartz score ≥3.5) and for cascade/variant‑specific testing of relatives once a pathogenic variant is identified; document Schwartz score, ECG/QTc, and family history.
- Provide Schwartz score, serial QTc measurements, and prior testing when submitting for coverage.
Prefer targeted testing first; document prior negative tests before genomic testing
When a clinical hypothesis exists start with targeted testing (single‑gene or appropriate multi‑gene panel) and reserve genomic testing (WES/WGS/whole mitochondrial sequencing) for when targeted approaches are nondiagnostic; document prior negative targeted testing in authorization requests.
- List prior single‑gene or panel results and rationale for proceeding to genomic testing.
Provide justification when ordering commercial multi‑gene panels
Prior authorization may be expected for commercial multi‑gene panels; include documentation justifying the clinical indication and how the panel result will affect management.
- Supply family/personal history and prior testing to support medical necessity for a commercial panel.
Follow condition‑specific testing sequence and document plan
Begin testing strategies as specified by condition — e.g., start with sequence analysis for AR in AIS or with deletion/duplication analysis for DMD and reflex to sequencing if negative; document the chosen testing sequence in the request.
- Explain stepwise strategy (which test first, reflex plan) in the authorization documentation.
Sequence FBN1 first; reflex to deletion/duplication analysis if negative
For Marfan syndrome, begin with FBN1 sequencing and perform deletion/duplication analysis only if sequencing is negative; include clinical diagnostic criteria and aortic Z‑score where applicable in the request.
- Provide aortic dilation Z‑score and note absence of known familial FBN1 mutation when applicable.
Require genetics specialist evaluation and counseling prior to WES
Before approving Whole Exome Sequencing, ensure the member has been evaluated by a Board‑Certified/Board‑Eligible Medical Geneticist and has received pre‑ and post‑test counseling by an independent qualified provider; document these evaluations in the PA submission.
- Include geneticist consultation notes and counseling documentation with the request.
Perform clinical evaluation (ECG/echo) before genetic testing for cardiac indications
Consider non‑genetic diagnostic or screening methods (e.g., ECG, echocardiography) for cardiomyopathies/arrhythmia syndromes before genetic testing; document results of these evaluations with the genetic test request.
- Attach ECG/echocardiogram reports or other relevant diagnostic studies to support testing.
Order PMP22 duplication/deletion testing first for suspected CMT1A
For Charcot‑Marie‑Tooth when clinical picture is consistent, recommend single‑gene PMP22 duplication/deletion testing first (accounting for common CMT1A) before broader panel testing; document EMG/nerve conduction studies and family history as applicable.
- Provide EMG/NCS reports or justify bypass when a strong familial mutation is known.
Consider SLCO1B1 testing before simvastatin when clinically indicated
For pharmacogenetic considerations (statin myopathy), SLCO1B1 single‑gene testing is the most supported test for simvastatin risk assessment; include clinical context and intended therapeutic implication when ordering.
- State the planned statin and how test results would alter drug selection or dosing.
Target genetic testing for nephrotic syndromes to specified high‑risk infants/children
For congenital or familial nephrotic syndromes, target genetic testing to infants with congenital presentation, those of Finnish descent, or with family history suggestive of familial disease; document age at onset and family history in the request.
- Include whether disease is steroid‑resistant and prior therapeutic trials/results.
Require index‑case testing for inherited HCM before relatives are tested
For inherited HCM, perform testing in at least one affected relative (index case) to document a pathogenic familial mutation prior to predisposition testing of at‑risk relatives.
- Document index‑case results and family relationships when seeking cascade testing coverage.
Perform and document clinical evaluation alongside genetic testing
Do not order routine genetic testing in isolation; genetic testing should accompany appropriate clinical evaluation (history, exam, investigations) and be documented to support the testing choice.
- Attach clinical evaluation, pedigree, and prior diagnostic study results to authorization requests.
Follow contracture testing results before or along with MH genetic testing
For malignant hyperthermia, contracture testing (CHCT/IVCT) is the reference standard; positive or equivocal contracture results should be followed by genetic testing, and documentation of contracture testing should be included with genetic testing requests when available.
- If contracture testing not feasible, document rationale for proceeding with genetic testing.
Use serial testing strategy and document prior non‑diagnostic results
Testing approaches should proceed from serial single‑gene testing, deletion/duplication analyses, and multi‑gene panels to genomic testing if prior approaches are nondiagnostic; document prior test sequence and results when requesting broader testing.
- Provide chronology of prior tests and negative/uncertain findings in the PA submission.
Obtain molecular testing prior to muscle biopsy in suspected OPMD
For Oculopharyngeal Muscular Dystrophy (OPMD), perform molecular testing of PABPN1 before invasive procedures (muscle biopsy); document molecular test results and indicate that biopsy will be deferred unless molecular testing is normal.
- Include PABPN1 testing plan and prior non‑invasive diagnostic findings in the request.
Document clinical features, pedigree, and conventional diagnostic results
Document clinical features, detailed family history/pedigree analysis, results of conventional diagnostic studies, and how the test result will impact management when ordering genetic testing; include these materials in authorization or coverage submissions.
- Attach pedigree, exam findings, and relevant diagnostic reports (ECG, imaging, EMG, biopsy, sweat tests, etc.).
Include clinical justification and specialist evaluation where required
Required documentation includes clinical findings, family history, and explicit evidence that testing will inform prognosis, treatment, or reproductive decisions; for some panels (e.g., IBMFS) include genetics specialist evaluation and consideration of alternative etiologies.
- For IBMFS panels, include evaluation by a Board‑Certified/Board‑Eligible Medical Geneticist.
Tests, Panels, and Indications Not Covered / Investigational
The policy identifies a large list of specific tests, panels, and indications that are not covered because they are considered experimental, investigational, or not supported by sufficient peer‑reviewed evidence. This includes numerous proprietary commercial panels, broad multi‑gene screening panels for population testing, whole‑genome/whole‑mitochondrial/whole‑transcriptome sequencing for many indications, and other named assays.
When a requested procedure or CPT/HCPCS code corresponds to an item on the investigational/not‑covered lists, coverage will be denied unless the requestor can document a policy‑specified, medically necessary indication or new evidence establishing clinical utility.
Certain specific tests are explicitly listed as investigational and therefore not covered. For example, Lynch syndrome mRNA sequence analysis (CustomNext + RNA, Ambry Genetics) is considered experimental and investigational because its clinical value has not been established.
Providers ordering germline testing for Lynch syndrome should instead follow the policy's recommended diagnostic pathway (tumor MSI/IHC screening and DNA sequence analysis of MLH1, MSH2, MSH6, PMS2, EPCAM where criteria are met).
The policy enumerates numerous named tests, commercial panels, and conditions considered investigational or of uncertain benefit. Examples include deCODE panels, EpiSEEK, Genesys Carrier Screening Panel, expanded/pan‑ethnic carrier screens, BreastNext, CancerNext and many other multigene commercial offerings. In many cases the policy notes lack of peer‑reviewed evidence demonstrating clinical utility and potential difficulties interpreting results from broad panels.
Broad panels and novel technologies (including whole‑genome, whole‑mitochondrial, and whole‑transcriptome sequencing for many indications) are listed among investigational methods when used outside defined, supported indications. Providers should document why a specific panel is required and how results will change management; otherwise these tests are prone to denial.
Genetic testing performed primarily to guide the medical management of individuals who are not Aetna members is excluded from coverage. Testing of non‑member samples will be considered only when all of the following are met: the information is needed to assess risk in the Aetna member; the information will be used in the immediate care plan for the Aetna member; and the non‑member's plan will not cover the test (a copy of the non‑member's denial letter must be provided).
The policy lists specific HCPCS and CPT codes that are identified as not covered for the indications listed in this CPB. Use of these codes for investigational or excluded indications may trigger denial. Examples and named proprietary code mappings are provided in the coding section; ordering providers should verify that the code matches a policy‑approved indication before submission.
If a requested code is among those flagged as not covered for the CPB indications, submit documentation demonstrating a policy‑defined medical necessity exception or alternative covered indication.
Several named proprietary commercial panels are explicitly listed as Not covered for the CPB indications. Examples called out by name include Coloseq, Panexia, the Genesys Carrier Screening Panel, and BrevaGen. These products lack supporting peer‑reviewed evidence for the CPB‑listed clinical scenarios and are therefore excluded unless specific covered indications apply.
When considering commercially branded panels, orderers should document why a named proprietary panel is necessary versus an alternative covered test or targeted approach.
For routine carrier testing for Tay‑Sachs and Sandhoff disease, the policy indicates that DNA‑based mutation analysis is not the primary covered method; biochemical enzyme testing (hexosaminidase A/B activity) is the principal diagnostic approach. Molecular testing is appropriate only when enzyme testing is inconclusive or to resolve pseudo‑deficiency, consistent with established guidelines.
Providers ordering carrier evaluation for these disorders should follow the biochemical first‑line testing approach described in the policy and reserve sequence analysis for the limited situations outlined.
The policy cautions that broad multi‑gene panels whose clinical utility has not been established may yield results of uncertain benefit and are frequently considered investigational or not medically necessary. Panels such as BreastNext and other expansive hereditary cancer or carrier panels are specifically discussed as lacking demonstrated clinical utility for some indications.
When a broad panel is requested, documentation should show that the panel's gene content and clinical application match a CPB‑approved indication or that targeted testing is inappropriate and that the broader panel is likely to change management.
Genetic testing for lactose intolerance (e.g., LactoTYPE) is listed as not supported by current evidence and is not indicated in routine clinical management. Current guidelines for lactose intolerance do not recommend genetic testing as part of standard care because results do not meaningfully alter management.
Providers should rely on established clinical and functional testing approaches for lactose intolerance rather than ordering genetic assays for routine diagnostic purposes.
Testing for common MTHFR variants to assess risk of hereditary thrombophilia is not recommended and is considered not medically necessary. UpToDate and ACMG guidance referenced in the policy state there is no clinical rationale to order MTHFR variant testing for venous or arterial thrombosis risk assessment in asymptomatic individuals.
Providers should not order MTHFR genotyping for routine thrombophilia evaluation; follow established ACMG/clinical guidance for testing indications such as Factor V Leiden or prothrombin G20210A when clinically appropriate.
Background and Rationale
Genetic testing establishes a molecular diagnosis when results will directly affect treatment, prognosis, or reproductive decisions. The policy emphasizes that testing is covered only when medical necessity criteria are met: the member shows clinical features or is at direct risk; results will directly impact care; a thorough clinical evaluation (history, physical, pedigree, genetic counseling, and conventional diagnostics) has been completed and a definitive diagnosis remains uncertain; and disease‑specific criteria are satisfied.
Because evidence is limited for many commercially available tests and panels, uses outside the policy's specific covered indications are generally considered experimental and investigational.
The policy contains an extensive list of tests and panels considered experimental and investigational for indications not specifically listed as medically necessary. This includes many branded panels, certain whole‑genome/mitochondrial/transcriptome approaches, and other technologies where peer‑reviewed evidence of clinical utility is insufficient.
Providers should review the policy's investigational lists before ordering; tests on those lists will generally be denied unless new validated evidence or a covered indication documented in the CPB applies.
Definitions and Key Terms
Eligibility Requirements and Condition-Specific Eligibility Notes
Eligibility for covered genetic testing typically requires documentation that the member meets condition‑specific clinical criteria, that a proband or affected family member has been evaluated where indicated, and that testing will inform diagnosis, management, or reproductive decisions. For example, panel testing for inherited bone marrow failure syndromes requires specialist evaluation and exclusion of alternative etiologies prior to panel ordering.
Many covered indications also require prior clinical testing steps (e.g., tumor MSI/IHC for Lynch syndrome, sweat chloride testing for CF) and may limit testing to targeted single‑gene or minimum‑content panels unless broader genomic testing is justified by the clinical scenario.
Additional eligibility expectations in the policy include specialist involvement for selected complex tests: Whole exome sequencing (WES) and some large multi‑gene panels typically require evaluation by a Board‑Certified/Board‑Eligible Medical Geneticist and pre‑/post‑test counseling by an independent qualified provider. Documentation should show that less broad testing is not appropriate and that WES will impact management.
For inherited bone marrow failure panels and other high‑impact tests, prior authorization is often required and the request should document that policy criteria are satisfied.
Some eligibility rules emphasize sequential testing. When a familial pathogenic variant is known, testing of at‑risk relatives should be targeted to that variant rather than performing broad panels. For disorders where a stepwise approach is specified (e.g., begin with sequencing and reflex to deletion/duplication analysis), adherence to that sequence is expected prior to pursuing broader testing.
Failure to perform recommended prior or diagnostic steps (index‑case testing, functional testing, or specialist evaluation) may result in denial of coverage for subsequent genetic requests.
Documentation requirements supporting eligibility include demonstration that an affected index case has been tested when appropriate (e.g., APC/FAP, HCM) and that results would change management for the member or relatives. For CF and other conditions, established diagnostic algorithms (including sweat testing, enzyme assays, or other functional tests) should be followed before extensive genetic sequencing unless the policy specifies otherwise.
Requests for panels or sequencing should include records of clinical evaluation, relevant laboratory/functional testing, pedigree information, and explanation of how results will alter care.
For high‑complexity tests like WES, the policy requires that the clinical presentation does not fit a well‑described single‑gene syndrome and that WES is likely to be more efficient than a series of single‑gene/panel tests. Pre‑ and post‑test counseling by an independent qualified provider and specialist evaluation are required components of eligibility.
When WES is considered, documentation must show that alternative targeted approaches were considered and that WES is expected to influence diagnosis or management.
Eligibility for panel testing frequently depends on the panel meeting a specified gene‑content minimum and matching a policy‑approved indication. Examples in the policy include panels that must include at least 10, 15, 60, or 100+ genes depending on the indication; inherited bone marrow failure panels must include sequencing of at least 30 genes.
Prior authorization reviewers will assess whether the chosen panel's gene list and testing method align with the CPB‑required minimum content for the named indication.
In many cases, prior testing results are required before proceeding to more extensive assays. Examples: for Tay‑Sachs carrier screening start with the recommended targeted mutation panel and proceed to sequencing only when indicated; for Marfan syndrome begin with FBN1 sequencing and add deletion/duplication testing only if sequencing is negative.
When prior testing requirements exist, the policy expects documentation of those prior results or a clear rationale why prior testing was not feasible.
Documentation, Counseling, and Pre/Post-Test Requirements
Perform pedigree analysis and provide genetic counseling
Pedigree analysis and genetic counseling are expected prior to testing; pre‑ and post‑test counseling by an appropriate independent provider is required for certain tests (e.g., WES) and recommended for cascade testing of adult relatives.
- Provide counseling notes or billing codes (96040, S0265) where relevant.
Use independent genetic counselors for pre/post‑test counseling
Pre‑ and post‑test counseling should be by an independent qualified provider (not an employee of the testing laboratory), such as a certified genetic counselor or qualified APGN, particularly for WES and cascade testing scenarios.
Document genetic counseling using listed counseling codes
Genetic counseling services are available under listed billing codes (96040, S0265); include counseling documentation when required by the policy or when ordering tests with significant familial implications.
- Use 96040 or S0265 to document counseling visits when applicable.
Provide counseling for relatives undergoing cascade testing
Pre‑ and post‑test genetic counseling is recommended for cascade testing of at‑risk adult relatives when a pathogenic/likely pathogenic variant has been identified in the family; document counseling and informed consent.
Counsel and document when ordering RNA (mRNA) testing for VUS resolution
RNA testing (mRNA sequence analysis) can change variant classification and clinical management for hereditary cancer gene VUS; ensure counseling is provided and document how RGT results will affect management.
- Include prior DGT results and rationale for RGT in the authorization request.
Obtain consent and plan for incidental findings when ordering NGS
When introducing NGS testing for learning disabilities or other contexts with potential incidental findings, obtain informed consent and document processes for handling incidental/unanticipated findings and post‑test counseling.
- Document informed consent addressing possible incidental findings and data handling plans.
Document Revisions and Dates
Policy effective date
Policy last reviewed
Next scheduled policy review
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.