ModifiedCentenePolicy N/A

Genetic Testing: Exome and Genome Sequencing for the Diagnosis of Genetic Disorders (coverage criteria)

Policy governing medical necessity criteria and coding for clinical exome (ES/WES) and genome (GS/WGS) sequencing, including rapid and reanalysis, for patients with suspected genetic disorders; applies to Centene-affiliated health plans and providers ordering genetic testing.

Policy Summary

PayerCentene

PolicyExome and Genome Sequencing for the Diagnosis of Genetic Disorders (coverage criteria)

Policy CodePolicy N/A

Change TypeCriteria revisioncoding additionsalignment to PLUGS/ACMG

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and document evaluation by a Medical Geneticist, Genetic Counselor, or Advanced Practice Nurse in Genetics when submitting requests for ES/GS (including rapid and reanalysis pathways).

SourceLink

POLICY UPDATE CHANGES

Updated Standard and Rapid sequencing criteria to better align with recent guideline recommendations and to remove/clarify burdensome language (e.g., replaced some 'Board Certified' wording, adjusted criteria phrasing).

Added PLUGS and ACMG-aligned clinical criteria (e.g., epilepsy, bilateral sensorineural hearing loss, intellectual disability, global developmental delay, multiple congenital anomalies, and multi-criteria pathways) as indications for ES/GS.

Added CPT codes 0425U and 0426U to the policy reference table and rapid genome sequencing criteria.

Added 'Genetic Counselor' as a role in the policy.

Removed 'Board Certified' and replaced with '(APGN)'.

Changed developmental delay definition to 'global developmental delay'.

Added CPT codes 0425U and 0426U to the policy reference table and criteria for Rapid Genome Sequencing.

Expanded Reanalysis of Exome or Genome Sequencing Data criteria to allow reanalysis prior to 18 months if new qualifying findings exist.

Rapid Exome/Genome Sequencing criteria updated: removed certain age-agnostic language and limited rapid testing to individuals 12 months of age or younger for some indications; added epileptic encephalopathy as eligible for Rapid Genome Sequencing.

Standard Exome and Standard Genome Sequencing criteria were mildly expanded to include bilateral sensorineural hearing loss of unknown etiology plus one other eligible clinical finding.

Criteria set name changed from 'Reanalysis of Whole Exome Sequencing Data' to 'Reanalysis of Exome or Genome Sequencing Data'.

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5test types addressed

≤12mrapid age limit

≈18mreanalysis timing

PLUGS 2023guideline cited

2new CPT codes added

V2.2024policy version

Coverage Criteria

Standard Exome Sequencing (Medically Necessary Criteria)

Standard exome sequencing (81415, 81416, 0214U, 0215U) is considered medically necessary when ALL of the following are met:

Standard ES entry criteria: A. The member/enrollee has not previously had genome sequencing

Standard ES entry criteria: B. Alternate etiologies have been considered and ruled out when possible (e.g., environmental exposure, injury, infection, isolated prematurity)

Standard ES entry criteria: C. Clinical presentation does not fit a well-described syndrome for which rapid single-gene or targeted multi-gene panel testing is available

Standard ES entry criteria: D. The member/enrollee's personal and family histories have been evaluated by a Medical Geneticist, Genetic Counselor or an Advanced Practice Nurse in Genetics (APGN)

Clinical findings (at least one required)

Findings list: 1. Unexplained epilepsy diagnosed at any age
Findings list: 2. Global developmental delay or intellectual disability with onset prior to age 18 years
Findings list: 3. At least one congenital anomaly (functional and/or structural)
Two-of list: 4. At least TWO of the following: a) Bilateral sensorineural hearing loss of unknown etiology; b) Symptoms of a complex neurological disorder (e.g., dystonia, hemiplegia, spasticity, epilepsy, myopathy, muscular dystrophy); c) Family history suggestive of a genetic etiology, including consanguinity; d) Clinical or laboratory findings suggestive of an inborn error of metabolism; e) Autism; f) Severe neuropsychiatric condition (e.g., schizophrenia, bipolar disorder, Tourette syndrome, self‑injurious behavior, reverse sleep‑wake cycles); g) Period of unexplained developmental regression (unrelated to epilepsy or autism)n>=2

Reanalysis (Medically Necessary Criteria)

Reanalysis of exome or genome sequencing data (81417, 81427) is considered medically necessary when ANY of the following are met:

Reanalysis criteria: A. The member/enrollee had exome or genome sequencing at least 18 months ago>=18 months since prior sequencing

Reanalysis criteria: B. The member/enrollee's phenotype has expanded to include clinical findings that were not present at the time of the initial analysis AND results of prior exome or genome sequencing do not explain these new clinical findings

Reanalysis may be approved prior to 18 months if new qualifying findings are present (per policy modification)

Rapid Exome Sequencing (Medically Necessary Criteria)

Rapid exome sequencing (81415, 81416), with trio testing when possible, is considered medically necessary when ALL of the following are met:

Rapid ES entry criteria: A. The member/enrollee is an acutely-ill infant (12 months of age or younger)<=12 months

Rapid ES entry criteria: B. The member/enrollee has not previously had genome sequencing

Rapid ES entry criteria: C. Alternate etiologies have been considered and ruled out when possible (e.g., environmental exposure, injury, infection, isolated prematurity)

Rapid ES entry criteria: D. Clinical presentation does not fit a well-described syndrome for which rapid single-gene or targeted multi-gene panel testing is available

Standard Genome Sequencing (Medically Necessary Criteria)

Standard genome sequencing (81425, 81426, 0212U, 0213U, 0265U) is considered medically necessary when ALL of the following are met:

Standard GS prerequisites: A. Alternate etiologies have been considered and ruled out when possible (e.g., environmental exposure, injury, infection, isolated prematurity)

Standard GS prerequisites: B. Clinical presentation does not fit a well-described syndrome for which rapid single-gene or targeted multi-gene panel testing is available

Standard GS prerequisites: C. The member/enrollee's personal and family histories have been evaluated by a Medical Geneticist, Genetic Counselor or an Advanced Practice Nurse in Genetics (APGN)

Standard GS clinical findings: D. The member/enrollee meets at least one of the following: 1) previously had uninformative exome sequencing AND ES reanalysis is not possible; 2) unexplained epilepsy at any age; 3) global developmental delay or intellectual disability with onset prior to age 18 years; 4) at least one congenital anomaly; 5) at least TWO of the following: bilateral sensorineural hearing loss of unknown etiology; complex neurological disorder symptoms; family history suggestive of genetic etiology including consanguinity; clinical or laboratory findings suggestive of an inborn error of metabolism; autism

Rapid Genome Sequencing (Medically Necessary Criteria)

Rapid genome sequencing (rGS) (81425, 81426, 0094U, 0425U, 0426U), with trio testing when possible, is considered medically necessary when ALL of the following are met:

Rapid GS entry criteria: A. The member/enrollee is an acutely-ill infant (12 months of age or younger)<=12 months

Rapid GS entry criteria: B. Alternate etiologies have been considered and ruled out when possible (e.g., environmental exposure, injury, infection, isolated prematurity)

Rapid GS entry criteria: C. Clinical presentation does not fit a well-described syndrome for which rapid single-gene or targeted multi-gene panel testing is available

Rapid GS entry criteria: D. The member/enrollee's personal and family histories have been evaluated by a Medical Geneticist, Genetic Counselor or an Advanced Practice Nurse in Genetics (APGN)

Standard ES/GS medical necessity

Covered when ALL of the following are met (PLUGS July 2023 guidance):

Overall PLUGS criteria: 1) The etiology of the patient's features is not known and a genetic etiology is considered a likely explanation based on listed findings; 2) Alternate etiologies have been considered and ruled out when possible; 3) Clinical presentation does not fit a well-described syndrome for which more targeted testing is available.

PLUGS July 2023 guidance

Key individual indications: a) Epilepsy of unexplained etiology at any age OR b) Confirmed bilateral sensorineural hearing loss of unknown etiology with unrevealing panel testing OR c) Intellectual disability diagnosed by age 18 (DSM-5) OR d) Global developmental delay (formal assessment, under age 5, delay in >=2 domains) OR e) Multiple congenital anomalies affecting unrelated organ systems OR f) At least TWO of the subcriteria (single organ system abnormality; autism; severe neuropsychiatric condition; complex neurological symptoms; family history suggestive of genetic etiology including consanguinity; unexplained developmental regression; lab findings suggestive of inherited metabolic disorder)

PLUGS enumerated criteria a-f and subitems

Rapid GS (acutely ill) criteria

Rapid genome sequencing covered for acutely-ill individuals when ALL of the following are met (PLUGS June 2022 guidance):

Rapid sequencing (acutely-ill) overall: 1) Etiology unknown and genetic etiology likely based on one of: multiple congenital anomalies affecting unrelated organ systems; epileptic encephalopathy; OR TWO of listed severe criteria (abnormality affecting at minimum a single organ system; symptoms of a complex neurological condition; family history suggestive of genetic etiology including consanguinity; laboratory findings suggestive of an inborn error of metabolism; abnormal response to standard therapy). 2) Alternate etiologies considered and ruled out when possible. 3) rGS is more efficient and economical than separate single-gene tests or panels for the differential diagnosis.

PLUGS June 2022 guidance

Reanalysis of sequencing data

Reanalysis and sequencing updates:

Reanalysis pathway: Policy expanded to allow reanalysis prior to 18 months if the patient has new qualifying findings (supported by PLUGS)prior to 18 months with new findings

Rapid sequencing age & indications: Rapid exome/genome sequencing is appropriate only for individuals 12 months of age or younger for specified acute indications; intellectual disability and autism were removed from rapid criteria for this age groupage <=12 months

Hearing loss expansion: Standard Exome and Standard Genome Sequencing criteria expanded to cover bilateral sensorineural hearing loss of unknown etiology plus one other eligible clinical findingbilateral SNHL + 1 other finding

Main criteria sets (summary of changes)

Policy contains distinct criteria sets for Standard Exome Sequencing, Standard Genome Sequencing, Rapid Exome Sequencing, Rapid Genome Sequencing, and Reanalysis of Exome or Genome Sequencing Data.

Reanalysis - early path: Reanalysis of exome or genome sequencing data may be approved prior to 18 months if the patient has new qualifying findings (supported by PLUGS)prior to 18 months with new findings

Rapid sequencing age & indications: Rapid sequencing is restricted to acutely-ill infants (<=12 months) for defined indications; certain diagnoses not diagnosable in this age group were removed from rapid criteriaage <=12 months

Standard sequencing hearing loss expansion: Standard Exome and Genome Sequencing criteria were expanded to include bilateral sensorineural hearing loss of unknown etiology plus one other eligible clinical findingbilateral SNHL + 1 other finding

Standard or repeat exome/genome sequencing is investigational / not covered for indications that do not meet the policy's specified medical necessity criteria. This includes use of standard ES/GS for screening of asymptomatic or healthy individuals and repeat standard sequencing when the request does not satisfy the criteria described in the Standard Exome or Standard Genome sections.

Coverage for ES/GS is excluded when the clinical presentation clearly fits a well-described syndrome for which targeted testing (single-gene or focused multi-gene panel) is available and appropriate. Per the policy, ES/GS should not be used as first-line testing in those situations until targeted testing has been considered or performed.

This policy is intended as a guide to medical necessity and does not override the terms, conditions, exclusions, or limitations in an individual member's coverage documents. Where state Medicaid coverage provisions conflict with this clinical policy, state Medicaid provisions take precedence.

Repeat standard exome or standard genome sequencing is considered investigational / not covered. The policy also limits rapid exome/genome sequencing to specific acute indications (generally for acutely ill infants ≤12 months) and removes certain diagnoses (e.g., intellectual disability, autism) from rapid testing criteria because they cannot be reliably diagnosed in that age group.

When a request does not meet the policy criteria (for example, if prior required testing steps or documented clinical findings are missing, or targeted testing would be more appropriate), the service is considered not medically necessary and may be denied. Operationally, providers should ensure documentation shows consideration/ruled-out alternate etiologies and that required genetics evaluation and clinical findings supporting coverage are included with the request.

This clinical policy is a guide to medical necessity and is not a guarantee of payment. Coverage determinations remain subject to the Health Plan's contractual coverage terms and applicable legal/regulatory requirements; services that do not meet the Health Plan's medical necessity criteria may be denied.

Covered Indications

PLUGS-aligned indications

PLUGS-aligned indications (examples reflected from PLUGS July 2023):

PLUGS indications: Unexplained epilepsy; confirmed bilateral sensorineural hearing loss with unrevealing panel testing; intellectual disability diagnosed by age 18 (DSM-5); global developmental delay under age 5 (delay in >=2 developmental domains); multiple congenital anomalies affecting unrelated organ systems; OR meeting at least TWO of the specified additional criteria

Aligned to PLUGS July 2023 guidance

Bilateral sensorineural hearing loss plus one other eligible clinical finding

Bilateral sensorineural hearing loss plus one other eligible clinical finding is now explicitly covered under ES/GS criteria:

Hearing loss expansion: Bilateral sensorineural hearing loss of unknown etiology plus one other eligible clinical finding qualifies for Standard Exome or Genome Sequencing per policy expansionbilateral SNHL + 1 other finding

Eligibility Requirements

A documented family history suggestive of a genetic etiology, including consanguinity, counts as one qualifying clinical finding toward meeting the policy's coverage criteria. Family history should be clearly documented and may be combined with other listed clinical findings to satisfy multi-criterion requirements (e.g., two-of rules).

Top-level eligibility requirements include: evaluation by a Medical Geneticist, Genetic Counselor, or Advanced Practice Nurse in Genetics (APGN); consideration and, when possible, exclusion of alternate non-genetic etiologies; and confirmation that the clinical presentation does not match a syndrome for which targeted testing is available.

For Standard Exome Sequencing, the member must not have had prior genome sequencing. For Standard Genome Sequencing, GS is covered if prior exome sequencing was uninformative and ES reanalysis is not possible or would not address newly emergent qualifying findings.

Operationally, eligibility determinations rely on documented clinical findings, prior testing history, and evidence of genetics evaluation. Providers must supply records demonstrating that required prerequisites (e.g., prior testing status, unrevealing panels when specified, and genetics consultation) are met to support coverage decisions.

Supplemental operational notes: the policy was revised to add an early reanalysis pathway allowing approval of reanalysis prior to 18 months when new qualifying findings emerge, and CPT codes 0425U and 0426U were added to the rapid genome sequencing reference table — providers should reference the policy coding table when requesting rapid GS.

Coding

Standard Exome CodesCPTCovered

81415	Exome sequencing (example standard/rapid)
81416	Exome sequencing (example duo/trio modifier or genomic comparator)
0214U	Proprietary code example for standard exome (Genomic Unity Exome Plus Analysis - Proband)
0215U	Proprietary code example for standard exome comparator (Duo/Trio)

Reanalysis CodesCPTCovered

81417	Reanalysis of exome or genome sequencing data (example)
81427	Reanalysis of exome or genome sequencing data (example)

Rapid Genome/Proprietary CodesCPTCovered

0094U	Rapid whole genome sequencing (proprietary example)
0425U	Rapid genome sequencing comparator (proprietary example)
0426U	Ultra-rapid whole genome sequencing (proprietary example)

Standard Genome CodesCPTCovered

81425	Genome sequencing (standard)
81426	Genome sequencing (trio/comparator)
0212U	Proprietary code example for standard genome (proband)
0213U	Proprietary code example for standard genome comparator
0265U	Proprietary code example for standard genome

Example ICD-10 CodesICD-10

F70-F79	ICD-10 code range examples referenced
F80.0-F89	ICD-10 code range examples referenced
Q00.0-Q99.9	ICD-10 code range examples referenced

Rapid sequencing CPT codes addedCPT

0425U	CPT code added to reference table (rapid sequencing)
0426U	CPT code added to reference table (rapid sequencing)

Added CPT Codes for Rapid Genome SequencingCPT

0425U	CPT code added to policy reference table (Rapid Genome Sequencing)
0426U	CPT code added to policy reference table (Rapid Genome Sequencing)

inv-23: Age for rapid sequencing — eligibility age limit (<= 12 months)

Rapid sequencing age limitAcutely-ill infants 12 months of age or younger are eligible for rapid exome or rapid genome sequencing (<= 12 months).

Rationale for age limitRapid workflows are intended for acutely-ill infants where faster diagnosis can change acute medical or surgical management; criteria restrict rapid testing to this age group to reflect diagnosability and guideline alignment.

Age-related removals from rapid criteriaBecause certain diagnoses (intellectual disability, autism) cannot be reliably diagnosed in infants <=12 months, they were removed from rapid sequencing criteria.

Provider Actions

Prior Authorization

Code-based prior authorization expectation — providers should expect PA and referenced codes

Providers should expect that certain exome/genome sequencing services require prior authorization and that referenced CPT codes in the policy may trigger PA review. Coding lists included in the policy are informational; inclusion does not guarantee coverage. Always verify current codes and PA processes with the member's Health Plan prior to submitting claims.

Prior authorization may apply to listed CPT codes (e.g., 81415, 81416, 81425, 81426, 0214U, 0215U, 0094U, 0425U, 0426U, 0212U, 0213U, 0265U).
Inclusion/exclusion of codes in this policy is not a guarantee of coverage.

Prior Authorization

Prior authorization required for rapid sequencing — PA required and CPT 0425U/0426U referenced

Rapid genome sequencing (rGS) and related rapid tests are subject to prior authorization. Providers should reference the policy's rapid sequencing criteria and include the appropriate CPT codes when requesting authorization.

CPT codes relevant to rapid sequencing include 0094U, 0425U, 0426U, and where applicable 81425/81426.

Not Covered

Repeat standard exome or standard genome sequencing when criteria are not met is considered not covered / investigational. Similarly, using ES/GS for screening of asymptomatic or healthy individuals is not covered. Rapid sequencing is limited to specified acute indications (typically acutely-ill infants ≤12 months) and is not indicated for routine or screening use.

ES/GS is not covered when the etiology is already known or when the clinical presentation fits a well-described syndrome for which a more targeted single-gene or multi-gene panel is available and appropriate. The policy directs use of targeted testing first in those circumstances.

Rapid exome sequencing criteria no longer list intellectual disability and autism as eligible indications for infants ≤12 months because these diagnoses cannot be reliably established in that age group; rapid testing is limited to acute indications appropriate for very young infants.

Definitions

Exome sequencing targets the protein-coding regions of the genome (the exome), which represent roughly ~1% of the genome but capture a large proportion of known heritable disease variants. Genome sequencing covers coding and noncoding regions and can detect larger structural variants and copy-number changes not always captured by ES. Rapid sequencing workflows provide accelerated results (often within days) for acutely ill infants where expedited diagnosis may alter management.

inv-37: Definition — Exome sequencing (ES/WES)

DefinitionExome sequencing (ES/WES): sequencing and copy number variant (CNV) analysis of the protein-coding regions (exons) of the genome (the exome, ~1% of the genome), capturing ~85% of heritable disease-causing variants.

Test scopeTargets protein-coding regions and includes CNV analysis within the exons; used when phenotype suggests a broad genetic etiology not explained by standard workup.

Clinical useOften used for patients with congenital anomalies, developmental delay, intellectual disability, or unexplained complex phenotypes where targeted testing is not appropriate.

inv-38: Definition — Genome sequencing (GS/WGS)

Policy Summary

PayerCentene

PolicyExome and Genome Sequencing for the Diagnosis of Genetic Disorders (coverage criteria)

Policy CodePolicy N/A

Change TypeCriteria revisioncoding additionsalignment to PLUGS/ACMG

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Rapid ES entry criteria: E. The member/enrollee's personal and family histories have been evaluated by a Medical Geneticist, Genetic Counselor or an Advanced Practice Nurse in Genetics (APGN)

Rapid ES clinical findings: F. The member/enrollee meets at least one of the following clinical findings: 1) unexplained epilepsy; 2) global developmental delay; 3) at least one congenital anomaly; or 4) at least TWO of a defined list (bilateral sensorineural hearing loss of unknown etiology; complex neurological disorder symptoms; family history suggestive of genetic etiology including consanguinity; clinical/lab findings suggestive of inborn error of metabolism; severe neuropsychiatric condition; period of unexplained developmental regression)n>=1

Trio testing is preferred when possible; intellectual disability and autism were removed from rapid criteria for infants ≤12 months

Rapid GS clinical findings: E. The member/enrollee meets at least one of the specified clinical findings (including severe neuropsychiatric conditions or unexplained developmental regression; epileptic encephalopathy is explicitly added as an eligible finding)n>=1

Trio testing preferred when possible; CPT codes 0425U/0426U added to rapid GS coding

Developmental delay definition changed to 'global developmental delay' for Standard and Genome criteria to align with guidelinesglobal developmental delay

Developmental delay clarification: The policy clarifies developmental delay as 'global developmental delay' to align with guideline definitionsglobal developmental delay

Epileptic encephalopathy added as eligible for Rapid Genome Sequencing

Epileptic encephalopathy has been added as an eligible clinical finding for Rapid Genome Sequencing:

Epileptic encephalopathy is an eligible clinical finding for consideration of Rapid Genome Sequencing in acutely-ill individuals per policy update

Aligned with PLUGS June 2022 and policy revision notes

PA must document acute/clinical criteria supporting rGS (e.g., acutely-ill infant status when required, alternative etiologies considered).

Prior Authorization

Prior authorization for Rapid Genome Sequencing — PA requirements and code list inclusion

Rapid genome sequencing (including ultra-rapid/STAT workflows) requires prior authorization when used for acutely ill patients and must meet the policy's clinical criteria. Include code-level detail in the PA submission.

Include applicable rapid sequencing CPT codes (0094U, 0425U, 0426U, and 81425/81426 where used).
Document why rapid turnaround is clinically indicated (e.g., critical newborn with unexplained features where rapid results would change management).

Documentation Required

Reanalysis before genome sequencing — genome sequencing after uninformative ES is covered when ES reanalysis is not possible

Reanalysis of prior exome/genome data is an available pathway before pursuing new genome sequencing when criteria are met. If reanalysis is not possible, standard genome sequencing may be considered per the policy.

Reanalysis (81417, 81427) is medically necessary when prior ES/GS was performed ≥18 months ago or when the phenotype has expanded to include new clinical findings not explained by prior results.
If reanalysis of exome data is not possible, Standard Genome Sequencing criteria may provide coverage.
Reanalysis is investigational for indications not meeting listed criteria.

Note

Testing approach for hearing loss — guidance on first-line GS for syndromic hearing loss vs tiered approach for non-syndromic

When evaluating hearing loss, follow specialty guidance: syndromic hearing loss may warrant first-line genome sequencing, while non-syndromic cases typically follow a tiered testing approach beginning with comprehensive hearing loss gene panels unless a specific etiology suggests targeted testing.

For exam findings suggestive of syndromic hearing loss, consider GS as first-line testing.
For isolated/non-syndromic hearing loss, begin with a comprehensive hearing loss gene panel; proceed to ES/GS if panel testing is unrevealing and criteria are otherwise met.

Documentation Required

Required clinical documentation — evaluation by Medical Geneticist/Genetic Counselor/APGN and alternate testing considered

Providers must document key clinical information to support medical necessity for ES/GS and related services. Documentation should demonstrate that alternate etiologies were considered and ruled out when possible, and that the member's personal and family history was evaluated by an appropriate genetics professional.

Evaluation by a Medical Geneticist, Genetic Counselor, or Advanced Practice Nurse in Genetics (APGN) is required and should be documented.
Clinical rationale must show why single-gene or targeted panel testing is not appropriate or has been unrevealing.
Document consideration and, when possible, exclusion of alternate etiologies (e.g., environmental exposures, infection, prematurity, MRI findings).
For ES/GS requests include relevant clinical findings that meet policy criteria (e.g., unexplained epilepsy, global developmental delay, congenital anomalies, multiple qualifying features).

Denial Risk

Investigational indications trigger denial risk — repeat ES/GS or non-covered indications likely denied

Requests that do not meet the policy's stated clinical criteria, repeat testing without new indications, or requests for indications labeled investigational are at high risk for denial. Ensure submitted documentation aligns with policy criteria and PLUGS/ACMG-aligned standards.

Repeat ES/GS without new qualifying clinical findings or outside specified intervals is likely to be denied.
Requests for indications explicitly described as investigational (see reanalysis and repeat testing sections) will be denied.
Provide clear documentation of new/newly documented clinical findings if seeking repeat or expedited testing outside standard intervals.

Denial Risk

Denial triggers — criteria not met per PLUGS/derived criteria or known etiology / targeted testing available

Denials commonly arise when policy criteria are unmet, a known etiology already explains the clinical presentation, or a targeted test is available and more appropriate. Before submitting, confirm that no single-gene or panel test would address the suspected diagnosis more directly.

Tests may be denied if a known genetic etiology has already been established or if targeted testing is available and appropriate.
Failure to document that alternate etiologies were considered and ruled out can result in denial.
Repeat standard genome sequencing and other scenarios marked investigational per the policy are denial triggers.

Note

Coverage terms — coverage decisions subject to contract exclusions and limits

Coverage determinations depend on the Health Plan's contractual terms and the member's benefit design. This policy provides medical necessity guidance but does not guarantee payment; always verify contract exclusions, limits, and state/federal precedence for Medicaid or Medicare.

Coverage is subject to the terms, conditions, exclusions, and limitations of the member's coverage documents.
For Medicaid members, state Medicaid provisions supersede when they conflict with this policy.
Review applicable NCDs/LCDs and Health Plan-level administrative policies prior to applying policy criteria.

Billing Rule

Claims and documentation expectations — follow Health Plan contractual terms; policy is a guide

Claims and supporting documentation should follow the member's Health Plan contractual processes and the payer's prior authorization and claims submission requirements. This policy is a guide to medical necessity and does not replace payer-specific billing rules.

Follow the Health Plan's contractual terms and PA/claims submission workflows when submitting requests and claims.
Include clinical notes, genetics evaluations, prior test results, and justification for test selection and urgency with PA submissions.
Coding in the policy is informational; verify code applicability with current coding resources and payer billing rules.

DefinitionGenome sequencing (GS/WGS): comprehensive sequencing of coding and noncoding regions of the genome; greater ability than ES to detect large deletions/duplications and provides broader diagnostic yield.

Test scopeSequences both coding and noncoding DNA across the entire genome and requires greater data analysis but less DNA preparation compared with ES.

Clinical useMay be used as a first- or second-line test for congenital anomalies or intellectual disability per ACMG guidance; considered when ES is uninformative or reanalysis is not possible.

inv-39: Definition — Rapid exome/genome sequencing (rES/rGS) — accelerated workflows

DefinitionRapid exome/genome sequencing (rES/rGS): accelerated sequencing workflows that return preliminary results typically in <7 days (final report typically <2 weeks) for urgent clinical scenarios.

Indicated populationIntended for acutely-ill infants or other urgent clinical scenarios where rapid diagnosis may change acute management.

Operational noteRapid ES and rGS should be used when clinical presentation does not fit a well-described syndrome amenable to targeted testing and when alternate etiologies have been considered.

inv-40: Definition — Global developmental delay (GDD)

DefinitionGlobal developmental delay (GDD): significant delay (>=2 standard deviations below the mean) in at least two developmental domains (gross/fine motor, speech/language, cognition, social/personal, or activities of daily living).

Age considerationsGDD terminology adopted to align with guidelines and policy revisions; applies especially for children under age 5 in certain criteria sets.

Clinical implicationGDD is a qualifying clinical finding for ES/GS coverage when documented by formal developmental assessment per policy guidance.

inv-41: Definition — Intellectual disability (ID)

DefinitionIntellectual disability (ID): defined per DSM-5 criteria and referenced guidance, typically described as moderate/severe/profound ID diagnosed by age 18 years for the purposes of coverage criteria.

Age thresholdID is considered an eligible finding for standard ES/GS when onset/diagnosis occurs prior to 18 years of age, per ACMG-aligned recommendations.

Clinical utilityID as defined may support ES/GS when alternate etiologies are considered and targeted testing is not appropriate.

inv-42: Definition — global developmental delay (repeated inventory entry)

Policy change notePolicy revised terminology from 'developmental delay' to 'global developmental delay' to align with guidelines and clinical director feedback.

Role in criteriaGDD is a listed qualifying clinical finding for standard ES/GS and may be age-restricted in rapid sequencing criteria per policy updates.

inv-43: Definition — rapid sequencing age limit (<=12 months)

Rapid sequencing age limitRapid exome or rapid genome sequencing is appropriate only for acutely-ill infants 12 months of age or younger (<= 12 months).

Supporting policy languageRapid ES criteria explicitly state: 'The member/enrollee is an acutely-ill infant (12 months of age or younger)'. Rapid GS criteria contain identical age-language.

Impact on indicationsCertain diagnoses (e.g., intellectual disability, autism) were removed from rapid criteria because they cannot be diagnosed reliably in infants <=12 months.