Centene genetic and molecular testing coverage update

Medical Necessity Coverage Criteria

Known Familial Variant Analysis

Targeted mutation analysis for a known familial pathogenic or likely pathogenic variant is medically necessary when ALL of the following are met:

Known familial variant criteria: A. The member/enrollee is 18 years or older if the condition is adult-onset; AND B. The member/enrollee has a close relative with a known pathogenic or likely pathogenic variant causing the condition; AND C. An association between the gene and disease has been established.

Targeted mutation analysis for a known familial variant of uncertain significance is considered investigational; targeted analysis for other indications is investigational.

Targeted Carrier Screening

Carrier screening via full gene sequencing or targeted mutation analysis is medically necessary when ALL of the following are met:

Carrier screening criteria: A. The member/enrollee is considering pregnancy or is currently pregnant; AND B. The genetic disorder is a recessive condition with childhood onset; AND C. One of the following: (1) the member/enrollee has a close relative with a known pathogenic or likely pathogenic variant associated with the disorder, OR (2) the member/enrollee's reproductive partner is a carrier for the genetic disorder, OR (3) the member/enrollee or reproductive partner are members of a population with carrier rate >=1%, OR (4) the member or reproductive partner has a first- or second-degree relative affected with the disorder.

Carrier screening for all other indications is considered investigational.

Single-gene or Multigene Panel Analysis

Single-gene or multigene panel testing is medically necessary when ALL of the following are met:

Panel testing criteria: A. The member/enrollee displays clinical features consistent with the suspected genetic condition; AND B. The diagnosis remains uncertain after appropriate clinical evaluation and other standard laboratory tests/imaging have been performed; AND C. The test has clinical validity; AND D. The test has clinical utility demonstrated by at least one of: determines therapeutic effectiveness/harm, directly impacts management, determines prognosis, or provides/refines estimates of natural history or recurrence risk; AND E. There is no known familial pathogenic or likely pathogenic variant for which targeted analysis would be more appropriate; AND F. Non-genetic causes for the clinical features have been ruled out; AND G. An association between the gene or panel and disease has been established.

Genetic testing via single-gene or multigene panel analysis is investigational for all other indications.

Prenatal Diagnosis for Single-Gene Disorders

Prenatal diagnostic single-gene testing is medically necessary when ANY one of the following parental/family conditions is present AND additional requirements are met:

Parental/family conditions (ANY one): 1. At least one biological parent has a known pathogenic variant for an autosomal dominant condition; OR 2. Both biological parents are known carriers of an autosomal recessive condition; OR 3. One biological parent is suspected or known to be a carrier of an X-linked condition; OR 4. History of a previous child with a genetic condition and suspicion of germline mosaicism.

In addition, the natural history of the disease must be well-understood with high likelihood of morbidity, and the genetic test must have adequate sensitivity and specificity with understood residual risk. Prenatal diagnosis for adult-onset single-gene disorders (e.g., hereditary cancer syndromes such as BRCA1/2) is not medically necessary. Variants of unknown significance (VUS) in prenatal diagnosis are investigational.

Tumor Biomarker Analysis

General tumor biomarker analysis is medically necessary when ALL of the following are met:

Tumor biomarker criteria: A. The member/enrollee has a confirmed neoplasm and/or malignancy; AND B. The test has clinical validity; AND C. The test has clinical utility demonstrated by at least one of: determines therapeutic effectiveness/harm, directly impacts management, determines prognosis, or provides/refines estimates of natural history or recurrence risk; AND D. Testing is performed in a CLIA-approved laboratory.

General tumor biomarker analysis is investigational for all other indications. See NCCN guidance for tumor molecular testing when results will affect management or eligibility for targeted therapy.

Oncology Algorithmic Tests

Oncology algorithmic testing is medically necessary when ALL of the following are met:

Oncology algorithmic criteria: A. The member/enrollee has a suspected or confirmed neoplasm and/or malignancy; AND B. The test has clinical validity; AND C. The test has clinical utility demonstrated by at least one of: determines therapeutic effectiveness/harm, directly impacts management, determines prognosis, or provides/refines estimates of natural history or recurrence risk.

Oncology algorithmic tests (MAAAs) combine multiple analytes and clinical data via an algorithm; they are investigational for all other indications.

Other Tests

Other genetic/molecular tests are medically necessary when ALL of the following are met:

Other test criteria: A. The member/enrollee displays relevant clinical features consistent with the intended use of the test; AND B. The test has clinical validity; AND C. The test has clinical utility demonstrated by at least one of: determines therapeutic effectiveness/harm, directly impacts management, determines prognosis, or provides/refines estimates of natural history or recurrence risk; AND D. Testing is performed in a CLIA-approved laboratory.

Other tests are investigational for all other indications. The ACCE model and published frameworks should be used to evaluate analytic/clinical validity and clinical utility.

General coverage criteria

Covered when testing demonstrates clinical validity and clinical utility appropriate to the clinical scenario and when pretest counseling/documentation is provided

General coverage principles: Test demonstrates analytic and clinical validity and clinical utility per accepted frameworks (e.g., CDC ACCE model); results will inform diagnosis, prognosis, treatment, reproductive planning, or enable at-risk family testing.

References include the CDC ACCE model and Burke et al. Clinical validity measures include sensitivity, specificity, positive predictive value, and negative predictive value.

Oncology testing: Somatic/tumor molecular testing is appropriate when the patient is a candidate for anti-cancer therapy or when identifying uncommon actionable genetic changes in tumors will affect management; oncology algorithmic tests may be considered for suspected or confirmed neoplasm if clinical validity and utility are present.

References: NCCN Occult Primary; Hayes et al.; AACC description of MAAAs.

Prenatal testing for adult-onset conditions is not recommended unless results will affect pregnancy or childhood management; pretest counseling with genetics expertise is recommended and should be documented.

References: NSGC position and ACOG guidance.

Prenatal diagnostic testing for adult-onset single-gene disorders (for example, hereditary cancer syndromes such as BRCA1/2) is considered not medically necessary when requested solely to determine fetal status for conditions that manifest only in adulthood. The policy explicitly states that prenatal diagnosis via amniocentesis, CVS, or PUBS for adult-onset single-gene disorders is not medically necessary. [[9]]

National Society of Genetic Counselors (NSGC) guidance notes that prenatal genetic testing for known adult-onset conditions is not recommended if pregnancy or childhood management will not be affected. NSGC further recommends that prospective parents meet with a genetic counselor or other genetics specialist prior to testing to discuss natural history, availability of interventions, ethical considerations including the child’s future autonomy, and potential for genetic discrimination. [[23]]

This clinical policy is a guide to medical necessity used to assist coverage decisions and benefit administration and does not supersede plan contract terms, exclusions, or limitations. When state Medicaid coverage provisions conflict with this clinical policy, the state Medicaid provisions take precedence. Providers and plan administrators should apply the policy consistent with member contracts and applicable legal and regulatory requirements. [[40]]

The policy restates that prenatal diagnostic testing for adult-onset single-gene disorders is not medically necessary. Prenatal diagnostic testing by amniocentesis, CVS, or PUBS for adult-onset single-gene disorders is explicitly classified as not medically necessary in the criteria. [[9]]

The policy removed a prior subjective coverage requirement that a genetic condition be 'associated with a significant health problem.' The updated approach emphasizes objective measures of clinical validity and clinical utility across criteria sets rather than that subjective threshold. [[33]]

Examples of Covered Indications

Covered test categories summary

Summary of covered test categories when medical necessity criteria are met:

Covered test categories summary: Familial known pathogenic/likely pathogenic variant testing; targeted carrier screening in pregnancy (full gene sequencing or targeted mutation analysis); single-gene or multigene panels for unresolved clinical diagnoses; prenatal diagnostic testing for specific parental carrier/pathogenic scenarios; tumor biomarker analysis for confirmed malignancy; oncology algorithmic tests for suspected or confirmed malignancy; and other tests with demonstrated analytic and clinical validity and clinical utility.

Each category is subject to the specific criteria outlined for that test type; tests not meeting criteria are investigational.

ACMG examples of clinical, family, and societal utility that support coverage

Examples of clinical, family, and societal utility that support coverage decisions (per ACMG and related guidance):

ACMG examples of utility: Diagnostic testing that informs causality, prognosis, or treatment; newborn screening for recommended conditions; patients with complex disorders (e.g., autism, intellectual disability); rare disorders diagnosed by cytogenetic or microarray methods; and cases where results enable family testing or reproductive decision-making.

Who Is Eligible for Testing

Eligibility for targeted familial variant testing requires documentation that a close relative has a known pathogenic or likely pathogenic variant in the relevant gene. For carrier screening in pregnancy, eligibility may also be met when the member or partner is from a population with a carrier rate ≥1%, when a reproductive partner is a known carrier, or when a first- or second-degree relative is affected. Providers should document family history and confirm the familial pathogenic/likely pathogenic variant when requesting targeted familial testing. [[6]][[7]][[22]]

For targeted familial variant analysis, the policy requires that the member be age ≥18 if the condition is adult-onset and that the member have a close relative with a known pathogenic or likely pathogenic variant; an established gene–disease association is also required. Targeted analysis for a familial variant of uncertain significance is considered investigational. [[6]]

No additional top-level eligibility details are provided in this placeholder section.

Provider Responsibilities and Operational Requirements

Documentation Required

CLIA Laboratory Requirement

Testing performed for tumor biomarker and other specified genetic or molecular tests must be performed in a Clinical Laboratory Improvement Amendments (CLIA)–approved laboratory. Tests from laboratories that are not CLIA-certified may be denied.

Applies to tumor biomarker analysis and other tests where CLIA approval is specified in the criteria.

Prior Authorization

Medical Necessity Guidance and Prior Authorization

This policy is a guide to medical necessity and is used to assist in making coverage decisions and administering benefits. Prior authorization may be required for oncology and molecular tests per the Health Plan's administrative policies when coverage depends on demonstrated clinical validity and clinical utility.

Verify member benefits and prior authorization requirements with the Health Plan before ordering testing.
Prior authorization may request documentation of clinical validity and clinical utility as described in the applicable criteria.

Exclusions and Investigational Indications

Any indication that does not meet the specified medical necessity criteria for the applicable test category is considered investigational and not covered. This includes tests outside the listed covered indications for targeted familial testing, carrier screening, single-gene/multigene panels, prenatal diagnosis, tumor biomarker analysis, oncology algorithmic tests, and other genetic/molecular tests. Providers should align requests with the stated clinical validity and clinical utility requirements to support coverage. [[12]][[8]][[10]][[11]][[6]][[7]]

Prenatal diagnostic testing for adult-onset single-gene disorders is explicitly listed as not covered / not medically necessary. The policy identifies prenatal diagnosis for adult-onset conditions (e.g., hereditary cancer syndromes such as BRCA1/2) as not medically necessary when requested for fetal testing. [[9]]

Professional society guidance (AAP/ACMG joint statement and NSGC positions) does not support routine carrier testing of minors for recessive conditions when carrier status has no medical relevance during childhood. Predictive testing of minors for adult-onset conditions is recommended to be deferred unless interventions in childhood would reduce morbidity or mortality. These positions support that routine carrier screening or predictive testing of minors without immediate clinical utility is not covered. [[22]][[23]]

Billing Codes and Clinical Validity Measures

No explicit CPT/HCPCS/ICD codes in this sectionmixed

No codes listed

Clinical validity measures

SensitivityAmong people with a specific condition, the proportion who have a positive test result (Table 9.15.1).

SpecificityAmong people who do not have the condition, the proportion who have a negative test result (Table 9.15.1).

Positive predictive value (PPV)Among people with a positive test result, the proportion who actually have the condition (Table 9.15.1).

Negative predictive value (NPV)Among people with a negative test result, the proportion who do not have the condition (Table 9.15.1).

Key Terms and Definitions

Germline vs Somatic

Germline variantA genetic alteration occurring in germ cells (egg or sperm) that is present in every cell of the body and can be passed to offspring.

Somatic variantA genetic alteration occurring in a subset of cells or tissues (e.g., tumor) that is not inherited and cannot be passed to offspring.

Clinical relevanceGermline testing typically informs inherited disease risk and family testing; somatic testing primarily guides tumor-directed therapy.

Clinical validity (definition)

DefinitionClinical validity describes the accuracy with which a test identifies a particular clinical condition, measured by sensitivity, specificity, positive predictive value, and negative predictive value.

PurposeUsed to determine how reliably a test can confirm or refute a suspected diagnosis (diagnostic performance).

Background and Scope

Genetic testing encompasses technologies to detect both germline and somatic variation for prevention, diagnosis, and treatment. Germline variants are heritable and present in all cells, while somatic variants are acquired in a cell population (for example, tumors) and are not inherited. Oncology-focused tests seek somatic or tumor mutations to guide targeted therapy, and algorithmic oncology tests combine biomarkers and clinical data to generate diagnostic, prognostic, or predictive information. [[2]][[3]][[11]][[12]]

Policy Updates and Revision History

2024-11material_change

Operational consolidation of Known Familial Variant criteria into this policy and rewording for clarity; subjective language such as 'significant health problem' removed to focus coverage on clinical validity and utility.

2024-04-24operational_update

Minor rewording and alignment across criteria sets; oncology algorithmic criteria expanded to include 'suspected neoplasm and/or malignancy' and coverage criteria updated to emphasize clinical validity and utility.

2024-11material_change_summary

OpenPayer

General Approach to Genetic and Molecular Testing