CurrentCentenePolicy N/A

Genetic Testing for General Approach to Genetic Testing (PDF)

Provides Centene-affiliated health plans' general medical necessity criteria for various classes of genetic and molecular tests (known familial variant analysis, targeted carrier screening, single-gene/multigene panels, prenatal diagnosis for single-gene disorders, tumor biomarker analysis, oncology algorithmic tests, and other tests) when no more specific policy applies.

Policy Summary

PayerCentene

PolicyGenetic Testing for General Approach to Genetic Testing (PDF)

Policy CodePolicy N/A

Change TypeRevisions (definitions, criteria updates, additions)

Effective DateN/A

Next Review DateN/A

Key ActionDocument clinical features, prior appropriate evaluation and family/pedigree information to meet medical necessity criteria.

SourceLink

POLICY UPDATE CHANGES

Overview, coding, reference-table, background and references updated; replaced 'coverage criteria' with 'criteria'.

For Single Gene or Multigene Panel Analysis: removed 'conventional diagnostic testing' and added 'clinical evaluation and other standard…'.

Added/updated definitions (clinical validity, clinical utility, algorithmic test) and moved/merged criteria across multiple genetic testing categories.

Oncology Algorithmic Tests criteria expanded to include suspected neoplasm and/or malignancy.

Updated definition of targeted prenatal screening to include full gene sequencing or targeted mutation analysis for pathogenic or likely pathogenic variants.

7Test categories covered with criteria

VUSVariants considered investigational for targeted testing

CLIACLIA requirement applies to tumor and other tests

MultipleCoverage categories updated

11References listed in part

Coverage Summary

Scope: This policy (CURRENT) provides Centene-affiliated health plans' general medical necessity criteria for seven classes of genetic and molecular tests: known familial variant analysis, targeted carrier screening, single-gene/multigene panels, prenatal diagnosis for single-gene disorders, tumor biomarker analysis, oncology algorithmic tests, and other tests. Coverage stance: these test categories are covered_with_criteria when the policy's specific medical necessity elements are met. The policy emphasizes evaluation of clinical validity and clinical utility, and notes that state regulations, Medicare NCDs/LCDs, and FDA approvals may affect final coverage determinations.

Key statistics and policy flags

Test categories covered with criteria7

Variants considered investigational for targeted testingVUS

CLIA requirement applies to tumor and other testsCLIA

Coverage categories updatedMultiple

References listed in part11

Policy stanceCovered with criteria

Date of last revision11/2024

Medical Necessity Criteria (by test category)

MEDICAL-NECESSITY CRITERIA (by test category)

General criteria concepts: These criteria provide a consistent, policy-level approach to assessment of genetic and molecular tests not otherwise specified in related, test-specific policies. They apply to germline and somatic testing and are intended to ensure testing is appropriate, analytically and clinically valid, performed in an accredited laboratory (e.g., CLIA-certified), and that results will inform clinical management or reproductive decision-making. Genetic counseling is recommended when testing is being considered. State regulations, national guidelines, Local Coverage Determinations (LCDs), National Coverage Determinations (NCDs), and FDA approvals may affect applicability and coverage.

General Criteria for Known Familial Variant Analysis for a Genetic Condition:

I. Targeted mutation analysis for a known familial variant for a genetic condition is considered medically necessary when ALL of the following are met:

- The member/enrollee is 18 years or older (if the condition is adult-onset), AND

- The member/enrollee has a close relative with a known pathogenic or likely pathogenic (P/LP) variant causing the condition, AND

Policy Concepts and Definitions

This policy articulates general, policy-level concepts used to assess genetic tests, centering on clinical validity (accuracy metrics such as sensitivity, specificity, PPV, NPV) and clinical utility (whether testing and subsequent interventions improve health outcomes and the balance of risks/benefits). It also defines algorithmic tests as assays that combine multiple analytes and clinical inputs via an algorithm to yield risk, prognostic, or treatment recommendations and recognizes gene expression profiling and multianalyte assays with algorithmic analysis as common methodologies. State regulations, National Coverage Determinations/Local Coverage Determinations, and FDA influence may necessitate additional review when applying these criteria.

Term	Definition
Clinical validity	Accuracy with which a test identifies a particular clinical condition; components include sensitivity, specificity, positive predictive value, and negative predictive value.
Clinical utility	Risks and benefits resulting from genetic test use; considers whether the test and subsequent interventions lead to improved health outcomes and what risks occur as a result of testing.
Algorithmic test	A test that combines biomarkers and clinical data into an algorithm to generate a disease risk assessment, prognostic result, or clinical recommendation for treatment.
Adult-onset condition	A condition in which signs, symptoms, or manifestations typically begin after age 18.
Recessive condition	A condition in which both copies of a gene have a mutation (autosomal recessive), or an individual with one X chromosome is hemizygous for a mutation resulting in an X-linked recessive condition.
Close relatives	First-, second-, and third-degree blood relatives on the same side of the family (first-degree: parents, siblings, children; second-degree: grandparents, aunts/uncles, nieces/nephews, grandchildren, half siblings; third-degree: great grandparents, great aunts/uncles, great grandchildren, first cousins).
Sensitivity	Among people with a specific condition, the proportion who have a positive test result.
Specificity	Among people who do not have the condition, the proportion who have a negative test result.
Positive predictive value	Among people with a positive test result, the proportion who have the condition.
Negative predictive value	Among people with a negative test result, the proportion who do not have the condition.

Provider Actions & Operational Requirements

Documentation Required

Establish clinical indications and family history

Document the member's clinical features, prior appropriate clinical evaluation and standard testing, and detailed family/pedigree information (including presence of known pathogenic or likely pathogenic familial variant or affected relatives). Include documentation of any prior evaluations and the pedigree to support medical necessity under the policy criteria.

Clinical features and prior evaluations
Standard laboratory tests/imaging results
Detailed family/pedigree including affected relatives and known familial variants

Documentation Required

Use CLIA-approved laboratories for tumor and other tests

Ensure that tumor biomarker testing and other applicable genetic/molecular tests are performed in a Clinical Laboratory Improvement Amendments (CLIA)–approved laboratory, as testing in a CLIA-approved lab is required for medical necessity in tumor and other test criteria.

Coding

No specific billing/coding list in this partmixed

No codes listed

No codes listed in this partmixed

No codes listed

Revision History

11/2024Non-materialLatest

Semi-annual review: Overview, coding, reference-table, background and references updated; replaced 'coverage criteria' with 'criteria'; added General Tumor Biomarker Analysis, Oncology Algorithmic Tests, and Other Tests; modified Single Gene or Multigene Panel language (removed 'conventional diagnostic testing' and added 'clinical evaluation and other standard…').

11/2024Non-materialLatest

Consolidation and moves: Several Known Familial Variant criteria were moved/consolidated into this policy; Targeted Carrier Screening criteria moved from Prenatal/Preconception policy; Prenatal Diagnosis for Genetic Conditions added (moved from GT: Prenatal Diagnosis policy).

Evidence & References

Key guideline sources informing the policy include position statements and guidance from the ACMG, NSGC, NCCN, ACOG, and the CDC/ACCE model; full bibliographic references and supporting literature are provided in the original policy document.

Policy Summary

PayerCentene

PolicyGenetic Testing for General Approach to Genetic Testing (PDF)

Policy CodePolicy N/A

Change TypeRevisions (definitions, criteria updates, additions)

Effective DateN/A

Next Review DateN/A

Key ActionDocument clinical features, prior appropriate evaluation and family/pedigree information to meet medical necessity criteria.

SourceLink

On This Page

- An association between the gene and disease has been established.

II. Targeted mutation analysis for a known familial variant of uncertain significance (VUS) is considered investigational.

III. Targeted mutation analysis for a known familial variant for a genetic condition is considered investigational for all other indications.

General Criteria for Targeted Carrier Screening:

Definition: Targeted carrier screening screens, via full gene sequencing or targeted mutation analysis, for a pathogenic or likely pathogenic variant in a gene associated with a specific genetic condition.

I. Carrier screening for a genetic disorder may be considered medically necessary when ALL of the following are met:

- The member/enrollee is considering pregnancy or is currently pregnant, AND

- The genetic disorder is a recessive condition with a childhood onset, AND

- 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 the reproductive partner are members of a population known to have a carrier rate ≥ 1% for the condition, OR

4. The member/enrollee or the member/enrollee's reproductive partner has a first- or second-degree relative who is affected with the genetic disorder.

II. Carrier screening for a genetic disorder is considered investigational for all other indications.

General Criteria for Single Gene or Multigene Panel Analysis:

Note: Testing should be performed in a CLIA-certified laboratory and other standard testing/evaluation should have been performed and been inconclusive before genetic testing.

I. Genetic testing via single-gene or multigene panel analysis may be considered medically necessary when ALL of the following are met:

- The member/enrollee displays clinical features of the suspected genetic condition, AND

- The diagnosis remains uncertain after appropriate clinical evaluation and other standard laboratory tests, imaging, or evaluations have been performed and are inconclusive, AND

- The test has clinical validity (demonstrates accurate determination of diagnostic, prognostic or clinical information), AND

- The test has clinical utility as demonstrated by at least ONE of the following:

1. The test will determine if a particular therapeutic intervention is effective or ineffective, or if a particular intervention may be harmful, OR

2. The test will directly impact the member/enrollee's clinical management, OR

3. The test will determine prognosis, OR

4. The test will provide or refine estimates of natural history, recurrence risk, or predicted course of the condition, AND

- There is no known pathogenic or likely pathogenic familial variant for which targeted analysis would be more appropriate, AND

- Non-genetic causes for the clinical features have been reasonably ruled out (e.g., infectious, toxic, environmental causes), AND

- An association between the gene or multigene panel and the disease has been established.

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

Prenatal Diagnosis for Single Gene Disorders (via amniocentesis, CVS, PUBS):

I. Prenatal diagnosis for single-gene disorders via amniocentesis, CVS, or PUBS may be considered medically necessary when ALL of the following are met:

- The member/enrollee meets any ONE of the following parental/family criteria:

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. The member/enrollee has a history of a previous child with a genetic condition and is suspected to have germline mosaicism, AND

- The natural history of the disease is well-understood with a high likelihood of significant morbidity, AND

- The genetic test has adequate sensitivity and specificity to guide clinical decision making and residual risk is understood.

II. Prenatal diagnosis for single-gene disorders via amniocentesis, CVS, or PUBS for adult-onset single-gene disorders (e.g., hereditary cancer syndromes such as BRCA1/2) is considered not medically necessary.

General Criteria for Tumor Biomarker Analysis:

Note: Tumor biomarker testing must be performed in an appropriately accredited laboratory (e.g., CLIA).

I. Tumor biomarker analysis may be considered medically necessary when ALL of the following are met:

- The specimen is from a suspected or confirmed neoplasm, AND

- The test has demonstrated clinical validity for the indicated tumor type, AND

- The test has clinical utility such that results will inform selection of targeted therapy, prognosis, or other management decisions that would change clinical care.

II. Tumor biomarker analysis is considered investigational for indications without demonstrated clinical validity or utility.

General Criteria for Oncology Algorithmic Tests:

I. Oncology algorithmic tests (including gene expression profiling, multimarker assays, or algorithmic risk models) may be considered medically necessary when ALL of the following are met:

- The member/enrollee has a suspected or confirmed neoplasm, AND

- The test has demonstrated analytical validity and clinical validity in the relevant tumor type/population, AND

- The test has clinical utility such that the result will change management (e.g., treatment selection, intensity of therapy, or prognostic stratification), AND

- Results are interpreted in context of clinical and pathologic features by an appropriate clinician.

II. Oncology algorithmic tests are considered investigational for indications lacking demonstrated clinical validity or utility.

General Criteria for Other Tests:

Note: Other genetic or molecular tests not otherwise specified should be performed in accredited laboratories (e.g., CLIA-certified) and supported by evidence of clinical validity and utility.

I. Such tests may be considered medically necessary when ALL of the following are met:

- The test has established clinical validity for the indication, AND

- The test has demonstrated clinical utility that will impact clinical management, diagnosis, prognosis, or reproductive decision-making, AND

- Alternative standard tests have been considered and do not adequately address the clinical question, AND

- Testing is ordered by an appropriate clinician and results will be used to guide patient care.

II. Other genetic or molecular tests are considered investigational for indications lacking sufficient evidence of clinical validity or clinical utility.

Verify CLIA approval for the performing laboratory prior to ordering

Prior Authorization

Refer to related specific policies when applicable

When a more specific Centene policy addresses the test (for example: prenatal cfDNA, prenatal diagnosis, hereditary cancer, oncology molecular analysis, oncology algorithmic testing, pharmacogenetics, exome/genome sequencing, etc.), follow the specific policy criteria. Note that some related specific policies may require prior authorization; check and obtain prior authorization when required.

Refer to listed related policies for test-specific criteria
Obtain prior authorization when required by the specific policy

Documentation Required

Avoid testing for VUS or adult-onset prenatal indications

Do not order targeted testing of familial variants of uncertain significance (VUS). Prenatal diagnosis for known adult-onset single-gene disorders is considered not medically necessary unless criteria specify otherwise. Testing for VUS or prenatal testing for adult-onset indications is investigational or not medically necessary per policy.

Avoid family testing for VUS unless reclassified to pathogenic/likely pathogenic
Prenatal diagnosis for adult-onset single-gene disorders via amniocentesis/CVS/PUBS is not medically necessary

Documentation Required

Assess clinical validity and utility

Confirm and document that the ordered genetic test has demonstrated clinical validity and clinical utility as defined by the policy (accuracy measures such as sensitivity/specificity/PPV/NPV and impact on management or outcomes). Tests lacking documented clinical validity or utility may not meet medical necessity.

Document evidence of clinical validity (sensitivity, specificity, PPV, NPV)
Document expected clinical utility (impact on management, prognosis, or therapy)

Documentation Required

Refer to applicable NCDs/LCDs for Medicare members

For Medicare members, review applicable National Coverage Determinations (NCDs) and Local Coverage Determinations (LCDs) and Medicare Coverage Articles before applying this policy's criteria, and document review as applicable.

Check relevant NCDs/LCDs for Medicare members
Document any Medicare determinations relied upon

Documentation Required

State Medicaid precedence

For Medicaid members, state Medicaid coverage provisions take precedence when they conflict with this clinical policy. Check and document applicable state Medicaid manual or provisions prior to applying this policy to Medicaid member cases.

Verify state Medicaid coverage provisions
Document any state-specific precedence or deviations

04/2024Non-material

Semi-annual review: Updated title to V1.2024; removed Policy Reference Table; added definitions for clinical validity, clinical utility, and algorithmic test; added General Tumor Biomarker Analysis, Oncology Algorithmic Tests, and Other Tests; updated background and references.

11/2024MaterialLatest

Coverage criteria refinement: Updated coverage criteria to assess for clinical validity and clinical utility across test categories; Oncology Algorithmic Tests criteria expanded to include 'suspected neoplasm and/or malignancy' in addition to confirmed neoplasm; removed subjective criterion 'The genetic condition is associated with a significant health problem or problems.'

11/2024MaterialLatest

Clinical scope changes: Removed age restriction for adult-onset single gene or multigene panel testing (requirement replaced with presence of clinical features); updated definition of targeted prenatal screening to include full gene sequencing or targeted mutation analysis for pathogenic or likely pathogenic variants; added definition for autosomal recessive condition.

The policy documents multiple content consolidations and relocations: several Known Familial Variant criteria were consolidated into this general policy from a separate policy; Targeted Carrier Screening criteria were moved from the Prenatal/Preconception policy; Prenatal Diagnosis content was added/moved into this policy; and language clarifications and minor rewording (for example, changes to prerequisites for panels and removal of certain age restrictions) were implemented during semi-annual reviews. These change notes indicate consolidation and alignment of criteria across related genetic testing policies.