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CurrentBlue Cross Blue Shield - NebraskaPolicy M.87

MA Specialty Testing: Nutrition and Metabolism (Preauthorization Required)

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This policy governs preauthorization and medical necessity criteria for genetic and metabolic laboratory testing related to nutrition and metabolism for Blue Cross Blue Shield - Nebraska members.

Policy Summary

PayerBlue Cross Blue Shield - Nebraska

PolicyMA Specialty Testing: Nutrition and Metabolism (Preauthorization Required)

Policy CodePolicy M.87

Change TypeNo material changes (administrative revision)

Effective DateMay 1, 2026

Next Review DateJan 1, 2027

Key ActionObtain preauthorization and submit both the procedure and corresponding diagnosis code when requesting coverage.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

M.87policy identifier

Preauth Requiredauthorization stance

~45covered disorders

>40genes listed

9procedure levels

Coverage Criteria

Initial Genetic Testing for Specific Metabolic Disorders

Genetic testing to establish or confirm diagnosis for listed metabolic disorders may be considered reasonable and necessary when clinical features consistent with the disorder are present.

Covered Indications for Specific Metabolic Disorders: Genetic testing to establish or confirm one of the listed metabolic conditions to guide management may be considered reasonable and necessary when the member demonstrates clinical features consistent with the disorder.clinical features consistent

List of example disorders provided in policy

Not Medically Necessary: MTHFR Variant Analysis

Tests considered not reasonable and necessary

MTHFR targeted variant testing: Targeted MTHFR variant analysis (e.g., 677T, 1298C) (81291) is considered not reasonable and necessary for all indications, including evaluation for thrombophilia or recurrent pregnancy loss, evaluation of at-risk relatives, and pharmacogenetic/drug metabolism testing.

Policy Summary

PayerBlue Cross Blue Shield - Nebraska

PolicyMA Specialty Testing: Nutrition and Metabolism (Preauthorization Required)

Policy CodePolicy M.87

Change TypeNo material changes (administrative revision)

Effective DateMay 1, 2026

Next Review DateJan 1, 2027

Key ActionObtain preauthorization and submit both the procedure and corresponding diagnosis code when requesting coverage.

SourceLink

On This Page

Covered gene examples by procedure level

Covered gene-level testing examples mapped to molecular pathology procedure levels

Level 8 gene examples: ABCC8, AGL, AHI1, ASPM, CACNA1A, CHD7, COL4A4, COL4A5 (duplication/deletion analysis noted for COL4A5), COL6A1, COL6A2, COL6A3, CREBBP, F8, JAG1, KDM5C, KIAA0196, L1CAM, LAMB2, MYBPC3, MYH6

Listed as examples under Molecular pathology procedure, Level 8

Level 9 gene examples: ABCA4, ATM, CDH23, CEP290, COL1A1, COL1A2, COL4A1, COL4A3, COL4A5, DMD, DYSF, FBN1, ITPR1, LAMA2, LRRK2, MYH11, NEB, NF1, PKHD1, RYR1, RYR2

Listed as examples under Molecular pathology procedure, Level 9

Covered Indications

Diagnostic genetic testing to establish or confirm a range of metabolic disorders

Genetic testing to establish or confirm one of the following metabolic conditions to guide management may be considered reasonable and necessary when the member demonstrates clinical features consistent with the disorder.

Diagnostic metabolic disorders list: Congenital adrenal hyperplasia (including 21-hydroxylase deficiency); congenital disorders of glycosylation; congenital hyperinsulinism; disorders of amino acid and peptide metabolism (e.g., glutaric acidemia type I, homocystinuria due to CBS deficiency, methylmalonic acidemia, propionic acidemia, maple syrup urine disease); disorders of biotin metabolism (e.g., biotinidase deficiency); disorders of carnitine transport and the carnitine cycle (e.g., CPT II deficiency, primary carnitine deficiency); disorders of copper metabolism (e.g., ATP7A-related disorders, Wilson disease); disorders of fatty acid oxidation (e.g., MCAD deficiency); disorders of galactose metabolism (e.g., galactosemia); disorders of glucose transport (e.g., Glut1 DS); disorders of phenylalanine/tyrosine metabolism (e.g., alkaptonuria, phenylalanine hydroxylase deficiency); disorders of porphyrin and heme metabolism (e.g., acute intermittent porphyria); fibrous dysplasia/McCune-Albright syndrome; glycogen storage disorders (e.g., GSD I, Pompe); hypophosphatasia; Kallmann syndrome; lysosomal storage disorders (e.g., Gaucher, Krabbe, MPS I/II, mucolipidosis IV); urea cycle disorders (e.g., OTC deficiency); malignant hyperthermia; SHOX deficiency disorders.clinical features consistent

List is not exhaustive; see policy for additional disorders and references

Inherited metabolic and other genetic disorders

Inherited metabolic and other genetic disorder examples: Examples include glycogen storage disease type 1a (G6PC), congenital adrenal hyperplasia (CYP21A2), maturity-onset diabetes of the young (CEL), various enzyme deficiencies and syndromic conditions referenced in the policy.

Examples drawn from code and Level descriptions in policy

Genetic testing (full gene sequence, duplication/deletion analysis, or multi-gene platforms) for listed genes associated with metabolic or related genetic disorders

Genetic testing (full gene sequence, duplication/deletion analysis, or multi-gene platforms) for listed genes associated with metabolic or related genetic disorders.

Level 8 and Level 9 gene testing: Full gene sequence, duplication/deletion analysis, or multi-gene platform testing for the genes listed under Molecular pathology procedure Level 8 and Level 9 (examples include but are not limited to ABCC8, AGL, AHI1, ASPM, CACNA1A, CHD7, COL4A4, COL4A5, COL6A1-3, CREBBP, F8, JAG1, KDM5C, L1CAM, LAMB2, MYBPC3, MYH6, ABCA4, ATM, CDH23, CEP290, COL1A1-2, COL4A1-3, DMD, DYSF, FBN1, ITPR1, LAMA2, LRRK2, MYH11, NEB, NF1, PKHD1, RYR1, RYR2).

Clinical indication by diagnosis should be present; specific genes mapped to procedure levels in policy

Coding and Procedure Levels

Not Covered / Not Reasonable and Necessary (example)CPTNot Covered

81291

MTHFR Variant Analysis

Covered / Example CPT codes for other metabolic disorder testingCPTCovered

81400	Other Covered Metabolic Disorders - example panel codes listed
81401	Other Covered Metabolic Disorders - example panel codes listed
81402	Other Covered Metabolic Disorders - example panel codes listed
81403	Other Covered Metabolic Disorders - example panel codes listed
81404	Other Covered Metabolic Disorders - example panel codes listed
81405	Other Covered Metabolic Disorders - example panel codes listed
81406	Other Covered Metabolic Disorders - example panel codes listed
81407	Other Covered Metabolic Disorders - example panel codes listed
81408	Other Covered Metabolic Disorders - example panel codes listed
81250	Other Covered Metabolic Disorders - single gene

Covered CPT Codes (examples at start of list)CPTCovered

81250	G6PC GENE ANALYSIS COMMON VARIANTS
81291	MTHFR GENE ANALYSIS COMMON VARIANTS
81400	MOLECULAR PATHOLOGY PROCEDURE LEVEL 1

Molecular Pathology CPT LevelsCPTCovered

81401	MOLECULAR PATHOLOGY PROCEDURE LEVEL 2
81402	MOLECULAR PATHOLOGY PROCEDURE LEVEL 3
81403	MOLECULAR PATHOLOGY PROCEDURE LEVEL 4
81404	MOLECULAR PATHOLOGY PROCEDURE LEVEL 5
81405	MOLECULAR PATHOLOGY PROCEDURE LEVEL 6
81406	MOLECULAR PATHOLOGY PROCEDURE LEVEL 7
81407	MOLECULAR PATHOLOGY PROCEDURE LEVEL 8
81408	MOLECULAR PATHOLOGY PROCEDURE LEVEL 9

Covered CPT Codes - Level 8 examplesCPTCovered

81408

MOLECULAR PATHOLOGY PROCEDURE LEVEL 8

Covered CPT Codes - Level 9 examplesCPTCovered

81408

MOLECULAR PATHOLOGY PROCEDURE LEVEL 9

Provider Actions / Prior Authorization

Prior Authorization

Preauthorization required for specialty nutrition/metabolism tests

Preauthorization is required for specialty nutrition and metabolism testing; examples of CPT codes subject to review include 81400–81408 and 81250 (example list in policy). Providers must obtain prior authorization before submitting these specialty tests for coverage review.

Example CPT codes listed: 81400, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408, 81250

Prior Authorization

Preauthorization required for listed CPT and gene analysis codes

Preauthorization is required for the listed molecular pathology CPT codes and specific gene analysis codes; when requesting review providers must submit both the procedure code and the corresponding diagnosis code.

Example procedure codes: 81400–81408 and 81250
Both a procedure code and a diagnosis code are required for submission

Prior Authorization

Preauthorization required for listed molecular pathology procedures

Preauthorization is required for the molecular pathology procedures listed in the policy, including higher-complexity Level 8 and Level 9 molecular pathology testing (e.g., CPT 81408 as an example).

Level 8 and Level 9 molecular pathology procedure examples are listed under the policy (CPT 81408 shown as a Level 8/9 example)

Note

Evaluation per General Approach to Laboratory Testing

Genetic tests for metabolic disorders that are not specifically discussed in this policy will be evaluated according to the General Approach to Laboratory Testing referenced in the policy.

Clinical features consistent with the suspected disorder will be required for medical necessity evaluation
See General Approach to Laboratory Testing (policy) and resources such as GeneReviews, OMIM, or Genetics Home Reference for disorder-specific clinical criteria

Note

Quick Code Search (provider note)

Quick reminder: use the policy's Quick Code Search to check whether a procedure and diagnosis code pair will be approved, denied, or held for review before submitting.

Enter the procedure code, then the diagnosis code, then click 'Add Code Pair' to see status

Note

Benefit determination note

Benefit determination is made according to the member’s applicable benefit contract; medical policies are used to administer plan benefits but do not constitute authorization, certification, or a contract for benefits.

Policies guide coverage decisions but final benefits depend on the terms of the applicable benefit contract

Documentation Required

Quick Code Search guidance

Use the Quick Code Search tool to verify whether a procedure/diagnosis pair is listed and to see if it will be approved, denied, or held for review prior to submission.

Enter procedure code first, then diagnosis code; the tool shows a dropdown for listed policy codes

Documentation Required

Procedure and diagnosis code pairing required

When submitting tests for review, include both the procedure code and the diagnosis code; submissions lacking a code pair may be held for review or not approved.

Enter at least the first three characters of the diagnosis code when using the Quick Code Search
Both procedure and diagnosis codes are required for code-pair validation

Documentation Required

Benefit determination note — policies do not equal authorization

Medical Policies are used in administering plan benefits and do not by themselves constitute authorization, certification, or a contract for benefits; benefit coverage is determined by the applicable benefit contract.

Physicians and other providers remain responsible for providing medical advice and treatment despite policy guidance

Denial Risk

Denied: MTHFR targeted variant analysis (81291)

Targeted MTHFR variant analysis (e.g., 677T, 1298C) billed as CPT 81291 is considered not reasonable and necessary for all indications (including thrombophilia evaluation, recurrent pregnancy loss, evaluation of at-risk relatives, and pharmacogenetic/drug metabolism testing) and would be denied.

Example denied procedure code: 81291 (MTHFR targeted variant analysis)

Denial Risk

Preauthorization required — lack may trigger denial or hold

Tests covered by this policy require preauthorization; failure to obtain preauthorization may result in the claim being denied or put on hold for review.

Obtain prior authorization before sending specialty nutrition/metabolism molecular pathology tests

Prior Authorization

Preauthorization required per policy title/heading

The policy heading and content indicate preauthorization is required for the specialty testing described; providers should follow the preauthorization process for tests under this policy.

Policy title: 'MA Specialty Testing: Nutrition and Metabolism (Preauthorization Required)'

Eligibility Requirements

No specific eligibility criteria are listed at the top level of this policy. Clinical eligibility for genetic testing is determined by the diagnostic indications and criteria described elsewhere in the policy, and requests should include pertinent clinical features to support medical necessity.

Additional eligibility requirements are not enumerated in this section of the policy extract. Providers should follow the policy’s stated coverage criteria and submit complete clinical information with any prior‑authorization request.

Definitions

MTHFR targeted variant analysis (definition and exclusion)

Targeted variantsMTHFR targeted variant analysis examples: 677T and 1298C.

Common billing codeFrequently billed as CPT 81291 (MTHFR variant analysis).

Coverage stanceConsidered not reasonable and necessary for all indications, including thrombophilia evaluation, recurrent pregnancy loss, evaluation of at-risk relatives, and pharmacogenetic/drug metabolism testing.

Molecular pathology procedure levels (81400–81408)

Scope by code rangeMolecular pathology procedure levels are represented by CPT 81400–81408 (Level 1 through Level 9).

Categorization basisLevels are categorized by increasing complexity and breadth: Level 1 for single-variant analyses up to higher levels for multi-exon or multi-gene sequence analyses and duplication/deletion testing.

Typical test types per levelIncludes single-gene common variant analysis (eg, 81250), targeted variant panels, full gene sequencing, duplication/deletion analysis, and multi-gene platform sequencing mapped to higher levels.

Molecular pathology procedure Level 8 and Level 9 (scope and examples)

Level 8 (definition)Example Level 8: analysis of 26–50 exons by DNA sequence analysis, mutation scanning, or duplication/deletion variants of >50 exons; may include sequence analysis of multiple genes on one platform.

Level 8 (examples)Example genes listed under Level 8 include ABCC8, AGL, AHI1, ASPM, CACNA1A, CHD7, COL4A4, COL4A5 (duplication/deletion noted), COL6A1, COL6A2, COL6A3, CREBBP, F8, JAG1, KDM5C, KIAA0196, L1CAM, LAMB2, MYBPC3, MYH6.

Level 9 (definition)Example Level 9: analysis of >50 exons in a single gene by DNA sequence analysis (full gene sequence of large genes).

Level 9 (examples)Example genes listed under Level 9 include ABCA4, ATM, CDH23, CEP290, COL1A1, COL1A2, COL4A1, COL4A3, COL4A5, DMD, DYSF, FBN1, ITPR1, LAMA2, LRRK2, MYH11, NEB, NF1, PKHD1, RYR1, RYR2.

Not Covered / Exclusions

Targeted MTHFR variant analysis (e.g., 677T, 1298C) billed as CPT 81291 is considered not reasonable and necessary for all indications and therefore is not covered under this policy.

Code‑pair review results for submitted procedure and diagnosis codes may result in approval, denial, or a hold for further review. This policy notes that specific tests may be approved, denied, or held based on submitted code pairs; the document extract does not list additional individual test exclusions beyond those specified elsewhere (for example, MTHFR).

Within the provided extract there are no additional explicit test‑level exclusions enumerated beyond the targeted MTHFR variant analysis; absence of a specific exclusion in this segment does not imply coverage and decisions are made per the policy and benefit contract.

Background

This policy addresses genetic testing to establish or confirm diagnoses of metabolic and nutrition‑related genetic conditions when test results would affect clinical management. It explains that many metabolic disorders (examples listed in the policy) may be reasonable to test for when clinical features are consistent with the disorder, while reiterating that targeted MTHFR variant testing is not considered medically necessary. The policy also emphasizes that requests require appropriate clinical documentation and that coverage determinations align with the terms of the member’s benefit contract.

MA Specialty Testing: Nutrition and Metabolism (Preauthorization Required)

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Coverage Criteria

Covered Indications

Coding and Procedure Levels

Provider Actions / Prior Authorization

Eligibility Requirements

Definitions

Not Covered / Exclusions

Background

Revision History