Verify CPT/HCPCS codes and obtain authorization as needed

Policy lists example CPT and HCPCS billing codes for exome, genome, reanalysis, rapid sequencing, mitochondrial testing, panels, CMA, methylation, and single-gene assays; inclusion or exclusion of codes in the policy does not guarantee coverage — verify coding and authorization requirements before ordering or claim submission.

• Examples include CPT/HCPCS codes for exome/genome (e.g., 81415, 81416, 81425, 81426, 0212U/0213U), reanalysis (e.g., 81417, 81427), mitochondrial assays (e.g., 81460, 81465), CMA/methylation/FISH codes, and unlisted molecular procedure codes.
• Providers must reference current professional coding guidance and plan authorization procedures prior to claim submission.

Obtain prior authorization with clinical-criteria documentation

Prior authorization is required for exome, genome, rapid sequencing, and many panel or single-gene tests; authorization requests must include documentation that the member meets the policy's specific clinical criteria.

• Standard ES: member must not have prior genome sequencing and must meet listed clinical criteria (see Standard Exome Sequencing section).
• Rapid ES/rGS: used for acutely ill infants ≤12 months and requires documentation of criteria and genetics evaluation.
• Standard/rapid GS: prior authorization required when criteria (including prior uninformative ES or specified clinical findings) are met.

Use correct procedure codes and include clinical justification in authorization

Prior authorization is required when ordering specified sequencing or deletion/duplication tests; use the appropriate panel or single-gene CPT code and reference the documented clinical criteria in the authorization.

• Example: CHD7 testing cited with CPT 81407 or 81479 — if a panel is performed, submit the appropriate panel code and supporting clinical documentation.
• For NF1/NF2 and other condition-specific sequencing/deletion-duplication analyses, include the policy-required clinical features with the authorization.

Authorize ES/GS/rGS only with documented genetics evaluation and alternate-etiology review

When exome or genome sequencing (standard or rapid) is being considered as a first- or second-tier test (e.g., pediatric congenital anomalies, DD/ID, acutely ill infants), obtain prior authorization and document that alternate etiologies were considered and genetics evaluation occurred.

• ACMG supports ES/GS as first- or second-tier for congenital anomalies or ID/DD with onset <18; PLUGS/NSIGHT2 support rapid sequencing for acutely ill infants.
• Authorization requests should document genetics professional evaluation and that single-gene/panel testing was not appropriate or was uninformative.

Order CMA as first-line for GDD/ID/ASD when causal diagnosis unknown

Chromosomal microarray (CMA) is the recommended first-tier diagnostic test for global developmental delay/intellectual disability or autism spectrum disorder when a causal diagnosis is unknown; order CMA prior to broad genomic sequencing when indicated and document accordingly for authorization.

• CMA is first-line per AAP and ACMG guidance for GDD/ID and ASD.
• Include documentation showing CMA was considered or performed when requesting subsequent testing if applicable.

Order tests only when policy clinical criteria are met

Order molecular and diagnostic genetic tests only when the member meets the policy's specified clinical diagnostic criteria; authorization and coverage require demonstration that listed clinical findings and evaluation requirements are satisfied.

• Example: Beckwith-Wiedemann diagnostic pathway requires at least one Tier 1 or Tier 2 clinical finding plus a qualifying molecular abnormality.
• Standard exome sequencing requires genetics evaluation and that the presentation does not fit a well-described syndrome amenable to targeted testing.

Prior authorization must reference the policy's sequencing/deletion-duplication CPT codes

Certain sequencing and deletion/duplication analyses reference specific CPT-level codes in the policy updates; ensure prior authorization uses the policy-referenced codes and include clinical criteria in the request.

• Revision notes reference use of CPT 81408 and other sequencing codes for NF1/NF2 criteria — verify current code language in the policy section when requesting authorization.
• When panels or single-gene tests are indicated, submit the appropriate CPT for the performed assay and not an example replacement code.

Follow plan-level prior authorization and coverage procedures

This policy is intended as a medical necessity guide to assist coverage decisions; prior authorization may be required per the health plan's procedures and coverage documents — follow plan-level authorization rules.

• Coverage is subject to the terms, conditions, exclusions, and limitations of the member's benefit plan and applicable state/federal requirements.
• If plan-level authorization or state Medicaid/Medicare NCD/LCD requirements apply, include those references as requested by the payer.

Prefer targeted testing first when phenotype fits known syndrome

Use targeted single-gene testing or multigene panels first when the clinical presentation fits a well-described syndrome; reserve exome/genome sequencing for presentations that do not fit available targeted testing or when prior testing is uninformative.

• Standard ES criterion C specifies sequencing reserved when presentation does not fit a syndrome with available single-gene or targeted panel testing.
• For suspected Noonan spectrum, multigene panel is preferred over serial single-gene testing (see Panel preferred block).

Follow sequential testing for Angelman/Prader-Willi (methylation → deletion → UPD → imprinting defect)

For Angelman/Prader-Willi evaluation follow a stepwise testing strategy: begin with SNRPN/UBE3A methylation analysis; if normal proceed to deletion analysis of 15q11-q13, then UPD analysis, and if still normal consider imprinting defect analysis.

• The policy lists the recommended testing sequence: methylation → deletion analysis → UPD analysis → imprinting defect analysis.
• Authorization should reflect prior step results when requesting subsequent tests.

Apply tiered testing (e.g., hearing loss panel before ES/GS when appropriate)

Use a tiered testing approach for conditions such as hearing loss: start with a comprehensive hearing loss gene panel when appropriate; consider ES/GS as first-line only for syndromic presentations per ACMG guidance.

• ACMG recommends tiered approach: syndromic findings may warrant ES/GS; nonsyndromic cases usually start with a comprehensive hearing loss panel.
• Document phenotype to justify panel versus ES/GS selection in authorization.

Follow mitochondrial testing pathway: mtDNA NGS → alternate tissue → nuclear panel → ES

For suspected primary mitochondrial disease follow a stepwise pathway: preferentially perform mtDNA genome NGS; if blood testing is negative but suspicion remains, test an alternate tissue (e.g., muscle or urine); consider nuclear gene panels and then exome if panels are negative.

• Mitochondrial Medicine Society recommends mtDNA NGS as preferred methodology and tissue-based testing when blood is negative due to heteroplasmy.
• When panels are negative, consider whole exome sequencing per the policy guidance.

Prefer multigene panel for Noonan/RASopathy over serial single-gene testing

When Noonan spectrum is suspected, prefer a multigene RASopathy panel as the first-line diagnostic approach rather than serial single-gene testing to improve efficiency and yield.

• GeneReviews and policy recommend multigene testing for Noonan/RASopathies; single-gene PTPN11 testing may be considered in select cost/efficiency contexts.
• Document clinical features supporting a RASopathy panel when requesting authorization.

Document pre- and post-test genetic counseling and patient preferences

Document pre-test and post-test genetic counseling that addresses the possibility of secondary findings, documents patient preferences (including opt-out), and outlines a plan for returning results; include this counseling in the medical record when requesting authorization.

• Policy strongly advises pre- and post-test genetic counseling and documentation of discussion about secondary/incidental findings and return-of-results plan.
• Evaluation by a Medical Geneticist, Genetic Counselor, or APGN is required prior to exome/genome testing per criteria.

Include prior testing, alternate-etiology review, and genetics evaluation in documentation

Provide required clinical documentation with authorization requests: include prior testing history, consideration and exclusion of alternate etiologies, evidence that the presentation does not fit a well-described syndrome amenable to targeted testing, and documentation of genetics professional evaluation.

• Standard ES/GS criteria require that alternate etiologies be considered and that personal/family histories be evaluated by a Medical Geneticist, Genetic Counselor, or APGN.
• If prior ES was uninformative and reanalysis is not possible, document those prior results when requesting genome sequencing.

Include clinical scores and specific feature documentation for score-based indications

When tests require specific diagnostic scores or features (e.g., Marfan systemic score ≥7, aortic root Z-score >2.0, cEDS major criteria), include the clinical score values and supporting exam or imaging findings in the request and medical record.

• FBN1/Marfan criteria: provide aortic root Z-score and systemic score calculation or ectopia lentis findings.
• cEDS: document skin hyperextensibility, atrophic scarring, and the presence of generalized joint hypermobility or at least three minor criteria and that the panel includes COL5A1/ COL5A2.

Document disorder-specific clinical features to support testing

Clinical documentation must demonstrate phenotype and specific clinical features consistent with the disorder being tested (e.g., listed major/minor features for TSC, NF1, NF2) to support medical necessity and authorization.

• TSC requests should list major/minor features present and include three-generation family history when applicable.
• NF1/NF2 requests must document the enumerated clinical features (e.g., café-au-lait macules, vestibular schwannomas) or tumor/pathogenic-variant findings.

Obtain and document a three-generation family history for TSC testing

When testing for TSC, obtain and document a three-generation family history to determine if additional family members are at risk and to support the testing rationale in authorization requests.

• International TSC Clinical Consensus Group recommends a three-generation family history for all individuals considered for TSC testing.
• Include family history details in the medical record submitted with the authorization.

Provide tumor findings or laboratory NF2 variant data and age-specific details for NF2 requests

Document clinical findings and laboratory identification when requesting NF2 testing, including tumor features (e.g., bilateral vestibular schwannomas) or identification of an NF2 pathogenic variant on tumor tissue; include age-specific presentations for pediatric cases.

• NF2 adult criteria include bilateral vestibular schwannomas or unilateral schwannoma plus ≥2 other listed tumor/cataract findings.
• If a tumor tissue NF2 pathogenic variant was identified, include the laboratory report in the authorization request.

Align documentation and authorization with plan-level and regulatory requirements

Follow plan-level administrative policies and applicable state or federal requirements when submitting documentation and authorization requests; reference state Medicaid manuals or Medicare NCD/LCDs if applicable.

• The policy is a medical necessity guide; actual coverage and authorization are governed by the member's benefit contract and applicable laws/regulations.
• Include any plan-required forms or references when requesting authorization.

Coding inclusion/exclusion in policy does not ensure coverage

Inclusion or exclusion of codes in the policy does not guarantee coverage; providers should verify current coding guidance and coverage before submitting claims to avoid denial.

• Policy notes that CPT codes included are informational only and that providers must reference up-to-date coding guidance prior to claim submission.

Do not request standard exome if prior genome sequencing was performed

Requests for standard exome sequencing will not meet the standard exome criteria if the member has previously had genome sequencing; document prior genome sequencing results and do not request standard ES as an alternative.

• Standard ES criterion A requires that the member has not previously had genome sequencing.
• If prior genome sequencing exists, consider reanalysis or document why genome sequencing is not sufficient per policy pathways.

Unsupported indications (isolated hypermobility, broad Autism/ID panels) may trigger denial

Tests ordered for indications outside the policy's listed medically necessary criteria (e.g., comprehensive connective tissue panel for isolated hypermobility/hEDS, broad Autism/ID panels for unsupported indications) may be denied — ensure indication matches listed criteria.

• Comprehensive connective tissue panels are not supported for isolated hypermobility or hEDS.
• Autism/ID multigene panels have insufficient evidence per Concert note and may be denied if requested broadly without guideline-supported indications.

Single-gene sequencing/deletion-duplication requests lacking required clinical criteria risk denial

Requests for sequencing and/or deletion/duplication analysis (e.g., TSC1/TSC2, NF1, NF2) that do not meet the listed condition-specific diagnostic criteria or lack supporting clinical features may be denied.

• TSC testing requires presence of ≥1 major feature or ≥2 minor features as enumerated in the TSC criteria.
• NF1 testing requires specific diagnostic features (e.g., ≥6 café-au-lait macules, ≥2 neurofibromas) or a parent with established NF1; NF2 testing requires tumor-based criteria or tumor tissue pathogenic variant.

Autism/ID multigene panels for unsupported indications risk denial

Autism/ID multigene panel requests lacking guideline support or submitted for broad/unspecified indications are at high risk for denial due to insufficient evidence and lack of professional society recommendations.

• AAP and other guidelines do not recommend routine use of ASD/ID multigene panels; CMA and Fragile X testing are guideline-recommended first-line tests.
• Concert note specifically states insufficient evidence to support the Autism/ID panel for all indications.

Missing required clinical criteria (e.g., BWS) may lead to denial

If required clinical diagnostic criteria are missing from the documentation (e.g., Beckwith-Wiedemann: no Tier 1 or Tier 2 finding plus molecular result), the request may be denied — include both clinical and molecular findings where the policy requires both.

• BWS requires ≥1 Tier 1 or Tier 2 clinical finding AND a molecular finding (abnormal methylation at 11p15.5, CNV at 11p15.5, or CDKN1C pathogenic variant) to establish diagnosis.
• Authorization should include explicit listing of the clinical tier findings and the molecular test result or prior test steps.

Coding/criteria changes in policy may cause denial if outdated codes/criteria used

Policy-wide removal or replacement of CPT/code references and changes to criteria language may affect previously accepted coding and could lead to denials if older codes or outdated criteria are used — confirm current policy code lists when ordering or billing.

• Revision notes indicate removal of prior example codes (e.g., 0214U/0215U) and addition/replacement with CPT codes (e.g., 81415/81416); use the policy's current code references.
• Older authorization or claim submissions using removed codes may be subject to denial.

Coverage decisions constrained by benefit documents and legal/regulatory requirements

Coverage and authorization decisions are subject to the member's benefit terms, exclusions, and state/federal requirements; if plan documents or legal/regulatory mandates conflict with the policy, those documents govern.

• The policy is a guide to medical necessity but does not guarantee payment; follow evidence of coverage, state Medicaid manuals, and Medicare NCD/LCDs as applicable.
• Include any plan- or state-required documentation when requesting authorization to avoid administrative denials.