CurrentUnitedHealthcarePolicy 2025T0589X

Whole Exome and Whole Genome Sequencing (Non-Oncology Conditions)

Coverage policy for outpatient whole exome sequencing (WES) and whole genome sequencing (WGS) for non-oncology conditions under UnitedHealthcare Commercial and Individual Exchange plans, including prenatal indications and limitations.

Policy Summary

PayerUnitedHealthcare

PolicyWhole Exome and Whole Genome Sequencing (Non-Oncology Conditions)

Policy CodePolicy 2025T0589X

Change TypeCode list update (added 0582U, 0583U)

Effective DateOct 1, 2025

Next Review Date

Key ActionWES or WGS must be ordered by an appropriate specialist and meet listed clinical criteria for coverage.

SourceLink

POLICY UPDATE CHANGES

Applicable CPT codes list updated to reflect quarterly edits and codes 0582U and 0583U were added.

Updated list of applicable CPT codes to reflect quarterly edits; added 0582U and 0583U

10/01/2025effective date

10/01/2025Summary of Changes date

>=18 moreanalysis interval

2CPT/PLA codes added

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Coverage Criteria and Clinical Evidence

Society guideline-based indications and prerequisites

Society guideline-based indications and prerequisites — recommendations from professional societies and guideline bodies relevant to clinical use of WES/WGS and related technologies.

European Society of Human Genetics (ESHG): - Recommend introducing diagnostic whole genome sequencing (WGS) when it represents a relevant improvement in quality, efficiency, and/or diagnostic yield over existing approaches. - Diagnostic WGS and other NGS-based testing should be performed only in accredited laboratories with appropriate validation and quality control. - Results obtained in a research setting should be confirmed and re-tested in a diagnostic laboratory before clinical reporting.

International Society of Prenatal Diagnosis (ISPD): - Do not support routine prenatal sequencing of fetal tissues obtained via invasive procedures (amniocentesis/CVS) in the absence of fetal anomalies. - Recommend prenatal genome-wide sequencing when current pregnancy demonstrates a major single anomaly or multiple organ system anomalies and when a genetic expert considers the phenotype suggestive of a genetic etiology. - Recommend CMA/karyotype be performed before or in parallel with prenatal exome sequencing; consider trio or affected-proband testing and multidisciplinary review for case selection. - Consider sequencing of parents (when proband sample not available) for identifying shared carrier status in suspected autosomal recessive etiologies; testing of tissue from a previously affected fetus/child is preferable when available.

National Institute for Health and Care Excellence (NICE, 2022): - Recommend consideration of whole genome sequencing for individuals with epilepsy of unknown cause when onset occurred in early childhood (approximately two to three years of age), particularly when evaluated and recommended by a specialist multidisciplinary team. - Recommend specialist discussion of uncertainties around genetic testing and use of national genomic testing guidance and comprehensive genetic counseling for patients and families.

National Society of Genetic Counselors (NSGC, 2022): - Strongly recommend that genetic testing (exome sequencing, exome-based gene panels, and/or multi-gene panels >25 genes) for unexplained epilepsy be selected, ordered, and interpreted by a qualified healthcare provider and accompanied by appropriate pre- and post-test genetic counseling. - Recommend ES/large panels or MGP as first-tier testing for individuals with unexplained epilepsy, followed by chromosomal microarray; conditionally favor exome-based panels over broader multi-gene panels.

Covered Indications for WES/WGS

Provider Actions, Documentation & Ordering Requirements

Billing Rule

Applicable codes listed and kept current

Specific CPT/PLA and proprietary molecular procedure codes applicable to WES/WGS are provided and may be updated quarterly. Use current codes when requesting authorizations and billing.

Verify and use the most current codes at time of request — UnitedHealthcare updated applicable codes on 10/01/2025 (added 0582U and 0583U).
List separately comparator exome/genome codes (e.g., 81416, 81426, 0336U, 0583U) when parental/sibling sequencing is performed.

Prior Authorization

Prior authorization / coverage access

Prior authorization may be required for WES, WGS, and rapid/ultra-rapid sequencing depending on the member's benefit plan. Coverage decisions must reference the member-specific benefit plan and applicable state or federal mandates.

Applicable Codes and Billing

Applicable PLA/CPT-Equivalent Codes (group 1)CPT

0094U	Genome (e.g., unexplained constitutional or heritable disorder or syndrome), rapid sequence analysis.
0212U	Rare diseases (constitutional/heritable disorders), whole genome and mitochondrial DNA sequence analysis, proband.
0213U	Rare diseases (constitutional/heritable disorders), whole genome and mitochondrial DNA sequence analysis, each comparator genome (e.g.; parent, sibling).
0214U	Rare diseases (constitutional/heritable disorders), whole exome and mitochondrial DNA sequence analysis, proband.
0215U	Rare diseases (constitutional/heritable disorders), whole exome and mitochondrial DNA sequence analysis, each comparator exome (e.g., parent; sibling).
0260U	Rare diseases (constitutional/heritable disorders), identification of copy number variations, inversions, insertions, translocations, and other structural variants by optical genome mapping.

Applicable PLA/CPT-Equivalent Codes (group 2)CPT

0264U	Identification of copy number variations, inversions, insertions, translocations, and other structural variants by optical genome mapping.
0265U	Rare constitutional and other heritable disorders, whole genome and mitochondrial DNA sequence analysis, multiple sample types, identification of single nucleotide and copy number variants.
0266U	Unexplained constitutional or other heritable disorders or syndromes, tissue-specific gene expression by whole-transcriptome and next-generation sequencing, reported as presence or absence of splicing or expression change.
0267U	Rare constitutional and other heritable disorders, identification of copy number variations and other structural variants by optical genome mapping and whole genome sequencing.
0335U	Whole genome sequence analysis including many variant types, fetal sample, identification and categorization of genetic variants.
0336U	Whole genome sequence analysis, blood or saliva, identification and categorization of genetic variants, each comparator genome.

Applicable PLA/CPT-Equivalent Codes (group 3)CPT

0425U	Genome rapid sequence analysis, each comparator genome (e.g., parents, siblings).
0426U	Genome ultra-rapid sequence analysis.
0454U	Identification of structural variants by optical genome mapping.
0469U	Whole genome sequence analysis for chromosomal abnormalities, fetal sample, diagnostic report with comparators.
0532U	Rapid whole genome and mitochondrial DNA sequencing for SNVs and indels, peripheral blood, buffy coat; saliva, buccal or tissue sample.
0567U	Whole-genome sequence analysis combining short and long reads for SNVs, indels, intronic variants, CNVs, mobile element insertions, ROH.

Applicable molecular/proprietary and CPT codesmixed

0264U	Rare diseases (constitutional/heritable disorders), identification of copy number variations, inversions, insertions, translocations, and other structural variants by optical genome mapping.
0265U	Rare constitutional and other heritable disorders, whole genome and mitochondrial DNA sequence analysis, blood; FFPE tissue, saliva, buccal swabs or cell lines, identification of single nucleotide and copy number variants.
0266U	Unexplained constitutional or other heritable disorders or syndromes, tissue-specific gene expression by whole-transcriptome and next-generation sequencing, blood, FFPE tissue or fresh frozen tissue, reported as presence or absence of splicing or expression change.
0267U	Rare constitutional and other heritable disorders, identification of copy number variations, inversions, insertions, translocations, and other structural variants by optical genome mapping and whole genome sequencing.
0335U	Rare diseases (constitutional/heritable disorders), whole genome sequence analysis, including small sequence changes, CNVs, deletions, duplications, mobile element insertions, UPD, inversions, aneuploidy, mitochondrial genome sequence analysis with heteroplasmy and large deletions, STR gene expansions; fetal sample, identification and categorization of genetic variants.
0336U	Rare diseases (constitutional/heritable disorders), whole genome sequence analysis, including small sequence changes, CNVs, deletions, duplications, mobile element insertions, UPD, inversions, aneuploidy, mitochondrial genome sequence analysis with heteroplasmy and large deletions, STR gene expansions, blood or saliva, identification and categorization of genetic variants.
0425U	Genome, rapid sequence analysis, each comparator genome (e.g., parents, siblings).
0426U	Genome, ultra-rapid sequence analysis.
0454U	Rare diseases (constitutional/heritable disorders), identification of copy number variations, inversions, insertions, translocations, and other structural variants by optical genome mapping.
0469U	Rare diseases (constitutional/heritable disorders), whole genome sequence analysis for chromosomal abnormalities, CNVs, duplications/deletions, inversions, unbalanced translocations, ROH, UPD, and aneuploidy, fetal sample; diagnostic report of fetal results with comparator maternal/paternal samples.

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Applicable CPT/HCPCS codes (updated)CPT

0582U	added — exact description not provided in this portion
0583U	added — exact description not provided in this portion

Applicable CPT/HCPCS codes updatedCPT

0582U	added code (as listed in summary of changes)
0583U	added code (as listed in summary of changes)

Age for highest detection probability in GDD cohort

Age range with highest detection probability12–24 months associated with highest probability of detection in the GDD cohort (Zhang et al. 2024).

Study populationProspective multicenter cohort of children aged 12–60 months with global developmental delay (Zhang et al. 2024).

Combined testing modalityTrio-WES performed with concurrent CNV-seq produced the reported detection rates in the study.

Definitions and Background Information

Whole Exome Sequencing (WES) analyzes the protein-coding regions of the genome (the exome), which represent roughly 1% of the genome but harbor a large proportion of disease-causing variants. Whole Genome Sequencing (WGS) determines the sequence of all nucleotides across the genome, including coding and noncoding regions and can detect SNVs, indels, CNVs, structural variants, mitochondrial variants, STR expansions, and some nonexonic regulatory/splicing variants.

The policy distinguishes these technologies in describing indications, comparative yields, and limitations (for example, detection differences driven by coverage and analytical methods) and notes that rapid/ultra-rapid sequencing modalities are intended for time-critical inpatient use.

WES definition

DefinitionWhole Exome Sequencing (WES) analyzes all exons (the protein-coding regions) of a person's DNA (the exome).

ScopeFocuses on regions where many disease-causing variants are found and sequences them simultaneously rather than gene-by-gene.

Clinical noteWES yields long lists of variants and depends on laboratory ability to identify disease-causing mutations for interpretation.

Services Not Covered / Considered Not Medically Necessary

The policy clarifies specific non-covered services: cell-free fetal DNA prenatal testing, preimplantation genetic testing (PGT) in embryos, evaluation of fetal demise, outpatient rapid/ultra-rapid sequencing, routine RNA sequencing (whole transcriptome), and whole genome optical mapping are listed among uses considered not covered or unproven under this policy.

These not-covered designations reflect the policy's synthesis of evidence reviews and professional guidance and are intended to guide provider ordering and payer adjudication for outpatient WES/WGS services.

Hayes clinical reviews cited in the policy indicate insufficient evidence of clinical utility for WES/WGS in certain pediatric neurological phenotypes and in some adult neurological populations. The policy uses these appraisals to limit routine coverage in contexts where improved clinical outcomes have not been demonstrated.

Providers should reference the policy coverage criteria and supporting evidence when requesting WES/WGS for neurological indications to ensure requirements are met.

Hayes evaluations summarized in the policy concluded there is insufficient evidence to support clinical utility of WGS (and in some cases WES) for several contexts, including routine prenatal application; these conclusions are cited as informing the policy's conservative stance where outcome data are lacking.

Such evidence summaries support the policy's position that WES/WGS outside defined indications may be considered not medically necessary.

The policy states that routine use of WES/WGS in prenatal screening or unselected pregnancies lacks sufficient evidence for demonstrated clinical utility, per Hayes reviews and other evidence summaries. Prenatal sequencing is therefore limited to fetuses with structural anomalies or after nondiagnostic CMA/karyotype when the phenotype suggests a genetic etiology.

Policy Revision History and Changes

2025-10-01codes_updatedLatest

Applicable CPT/HCPCS codes list updated to reflect quarterly edits; codes 0582U and 0583U were added.

The policy's Summary of Changes dated 10/01/2025 documents updates to applicable procedure coding, including the addition of codes 0582U and 0583U, and notes archival of the previous policy version. Providers are advised to use the updated code set when submitting requests or prior authorization.

The document includes multiple CPT/PLA and CPT-equivalent codes for WES/WGS and related procedures; providers should verify and apply the current codes listed in the policy and in payer claim systems.

The policy lists applicable CPT/HCPCS/PLA codes for exome and genome sequencing and related procedures and notes that codes 0582U and 0583U were added in the 10/01/2025 update. These codes should be used where appropriate when requesting authorization or submitting claims.

The policy's coding tables include a mix of proprietary PLA codes and standard CPT codes (for example, 81415–81417 for exome services and 81425–81427 for genome services) alongside the rapid/optical mapping and other specialized codes.

Policy Summary

PayerUnitedHealthcare

PolicyWhole Exome and Whole Genome Sequencing (Non-Oncology Conditions)

Policy CodePolicy 2025T0589X

Change TypeCode list update (added 0582U, 0583U)

Effective DateOct 1, 2025

Next Review Date

Key ActionWES or WGS must be ordered by an appropriate specialist and meet listed clinical criteria for coverage.

SourceLink

On This Page

Confirm prior authorization requirements with UnitedHealthcare before ordering.
Lack of prior authorization or benefit exclusion may result in claim denial or patient financial responsibility.

Documentation Required

Laboratory accreditation and validation

Testing should be performed only in clinical diagnostic laboratories with appropriate accreditation (e.g., CLIA, CAP) and acceptable analytic validation of the specific WES/WGS assay.

Do not submit results from research laboratories for diagnostic coverage without re-testing in an accredited diagnostic laboratory.
Labs must perform and document validation studies for the platform and report performance metrics (coverage, sensitivity for CNV/SV detection where claimed).

Billing Rule

Use updated applicable procedure codes

Use the updated procedure and PLA codes when requesting authorization or submitting claims; verify quarterly CPT/PLA edits as codes may change.

Providers are responsible for using current codes; outdated codes may delay authorization or reimbursement.
Contact UnitedHealthcare or check payer coding resources if a code is not recognized.

Billing Rule

Applicable codes updated

The policy lists updated and additional applicable codes; providers must verify coding and any associated billing instructions prior to submission.

Newly added codes (e.g., 0582U, 0583U) were included in the 10/01/2025 update.
When ordering rapid or comparator testing, include both primary and comparator codes as appropriate (list separately when required).

Denial Risk

Denial triggers for unsupported indications

Requests that do not meet the specified clinical criteria or that seek testing in unsupported indications may be denied.

Unsupported indications include prenatal testing via cell-free fetal DNA, evaluation of fetal demise, preimplantation genetic testing (PGT), and routine screening when criteria are not met.
Outpatient rapid/ultra-rapid sequencing requests may be denied (not supported in outpatient setting).

Note

Provider actions — general guidance

Some provider actions are not explicitly specified in this excerpt; follow the policy's documentation, ordering and prior authorization guidance and consult UnitedHealthcare for any case-specific questions.

When in doubt, submit clinical records demonstrating how the member meets the policy criteria and request preauthorization if required.

Prior Authorization

Setting limitation for rapid sequencing

Rapid and ultra-rapid sequencing (rWES, rWGS, urWGS) are supported only for critically ill infants in an inpatient setting; use in outpatient settings is not supported.

Order rapid sequencing only when the patient is a critically ill infant in the NICU/PICU and clinical criteria are met.
Outpatient requests for rapid or ultra-rapid turnaround are not supported and are likely to be denied.

Prior Authorization

Setting-based coverage limitation

Reiterating setting-based coverage limitation: rapid/ultra-rapid tests are limited to inpatient critically ill infants; ensure documentation of inpatient status and clinical acuity when requesting these services.

Include unit/location (NICU/PICU), clinical severity, and rationale for expedited testing in the request to support medical necessity.

Documentation Required

Family testing and documentation

Family (trio or parental) testing often improves diagnostic yield and aids interpretation; documentation of family relationships and comparator samples should be provided when ordering trio or parental sequencing.

When ordering comparator sequencing, include separate codes for each comparator (e.g., 81416, 81426, 0336U, 0583U) and indicate relationship (mother, father, sibling).
Provide pedigree information and prior family test results to assist laboratory interpretation.

Documentation Required

Prenatal testing and documentation

For prenatal/fetal sequencing, document prior testing (e.g., negative NIPT, FISH, rapid karyotype, CMA) and rationale for fetal WES/WGS; in many cases CMA or karyotype should be performed before or in parallel with prenatal exome sequencing when multiple anomalies are present.

Include results of NIPT, FISH, CMA/karyotype and note whether maternal cell contamination has been excluded.
If parental samples or prior affected proband tissue are available, include these for trio analysis and cite reason for prenatal sequencing.

Documentation Required

Provider documentation and information sharing

Provide detailed clinical information and phenotype (e.g., HPO terms, three-generation pedigree, prior test results, onset age) to the laboratory to support interpretation and variant classification.

Attach relevant clinical notes, imaging reports, prior genetic test reports (CMA, targeted panels), and family history when submitting testing orders.
Document why WES/WGS is preferred over targeted testing in this member's clinical scenario.

Documentation Required

Targeted testing prior to WES/WGS

When a specific syndrome is suspected, perform targeted single-gene testing or a focused multi-gene panel as the initial test prior to WES/WGS to avoid unnecessary broader testing.

Document the clinical suspicion and why targeted testing is insufficient if proceeding directly to WES/WGS.
If targeted testing is negative or nondiagnostic, include those results with the WES/WGS request.

Note

Provider actions — none specified

No additional provider actions were specified in this excerpt beyond the ordering, documentation, coding, and prior authorization requirements summarized here.

Follow the policy criteria, provide required documentation, and contact UnitedHealthcare for clarifications.

Documentation Required

First-tier testing implication

Evidence and guideline statements indicate that exome sequencing (ES) may be appropriate as a first-tier test for certain neurodevelopmental disorders (e.g., ID, GDD, ASD) and some congenital anomalies; document rationale if ES/WGS is being used as first-line testing.

If ordering ES as first-tier, include clinical justification referencing neurodevelopmental phenotype or multiple congenital anomalies.
Provide prior testing performed (or rationale for skipping CMA) when applicable.

Documentation Required

Reanalysis before WGS

Consider reanalysis of previously obtained exome data before pursuing WGS, since reanalysis may reveal diagnoses with updated knowledge; if WGS is ordered after nondiagnostic WES, include prior WES VCF or reports when available.

Submit prior WES raw data or VCF and report when requesting WGS to allow comparison and avoid redundant testing.
Document the reason for WGS after nondiagnostic WES (e.g., detection of intronic/CNV/SV variants not assayed by WES).

Documentation Required

Tiered testing approach for hearing loss

For hearing loss, follow a tiered testing approach: start with a comprehensive hearing-loss genetic panel and, if negative, consider genome-wide testing such as ES or GS; ensure the chosen panel includes clinically relevant genes.

Document results of comprehensive hearing-loss panel and rationale for escalation to ES/WGS if panel is nondiagnostic.
Include audiology results, onset timing, and syndromic features in the submission.

Documentation Required

Chromosomal microarray prior to pES when indicated

When multiple fetal anomalies strongly suggest a chromosomal abnormality, perform chromosomal microarray (CMA) before or in parallel with prenatal exome sequencing (pES) per ISPD recommendations.

Provide CMA/karyotype results or document why CMA cannot be performed when requesting prenatal ES.
If CMA is negative and phenotype remains suggestive, include that in the rationale for pES.

WGS definition

DefinitionWhole Genome Sequencing (WGS) determines the sequence of all of the DNA in a person, including both coding (exons) and non-coding regions.

Detection capabilitiesCan detect SNVs, indels, copy number variants, structural variants, repeat expansions, and nonexonic regulatory/splicing variations.

Interpretation noteWGS produces large numbers of variants and uses similar interpretation methods and databases as WES but provides broader genomic coverage.

Comparator

DefinitionComparator: a DNA sequence used to compare to the individual's sequence (for example, parent or sibling DNA).

Typical useComparator samples (parents/siblings) are used to help interpret variant inheritance and improve diagnostic yield (trio testing).

ExampleParent or sibling DNA may be sequenced concurrently or previously as a comparator to the proband.

WES (alternate chunk)

Alternate wording (WES)WES refers to the sequence determination of the exome, the portion of the genome where disease-causing variants are often found; sequencing all exons at once is more efficient than gene-by-gene testing (Bertier et al., 2016).

Analytic focusTargets the protein-coding regions (exons) across the genome rather than individual genes.

Interpretation challengeWES generates lengthy variant lists requiring robust laboratory interpretation and classification.

WGS (alternate chunk)

Alternate wording (WGS)WGS determines the order of all nucleotides in an individual's DNA and can detect copy number variants (CNVs), structural variations (SVs), repeat expansions, and nonexonic regulatory/splicing variations.

Analytic breadthProvides potential to detect variant types beyond exons that may be missed by exome sequencing.

Interpretation noteWGS yields long variant lists and relies on the same interpretation frameworks as WES, with increasing clinical availability.

Whole transcriptome sequencing

DefinitionWhole transcriptome sequencing (RNAseq) analyzes all RNA transcripts in a tissue to identify coding and noncoding RNA differences, including aberrant expression or splicing.

Clinical roleRNAseq can add diagnostic information beyond DNA sequencing, particularly for splicing or expression abnormalities when DNA testing is nondiagnostic.

Evidence statusCurrent evidence is limited; RNAseq is not yet supported for routine diagnostic use due to small sample sizes and generalizability concerns.

Optical genome mapping (OGM)

Technology descriptionOptical genome mapping (OGM) images ultra-long single DNA molecules to construct genome maps that identify structural variants including insertions, deletions, duplications, inversions, and translocations.

Comparative capabilityOGM can detect structural variants not easily resolved by standard cytogenetics and may identify balanced SVs and precise locations/orientations of insertions/duplications.

Evidence statusOGM is investigational with early proof-of-principle studies; additional clinical utility studies are needed before clinical implementation.

Neurodevelopmental disorders (NDD)

DefinitionNeurodevelopmental disorders (NDD) are defined in cited reviews as global developmental delay (GDD), intellectual disability (ID), and/or autism spectrum disorder (ASD).

Clinical scopeNDD encompasses heterogeneous presentations including isolated or syndromic forms and may co-occur with other congenital anomalies.

Testing implicationES/WGS diagnostic yields vary by phenotype within NDD; yields are generally higher with associated features and when trio testing is used.

Rapid/Ultra-rapid genomic sequencing

DefinitionRapid and ultra-rapid genomic sequencing are expedited-turnaround NGS tests developed to provide timely diagnoses for critically ill infants.

Intended useDesigned for inpatient NICU/PICU settings where a rapid molecular diagnosis may affect immediate management; outpatient use is not supported.

Turnaround rationaleStandard NGS turnaround (weeks–months) is too slow for many critically ill infants, motivating development of rWES/rWGS/urWGS.

rWES, rWGS, urWGS

rWESRapid whole exome sequencing (rWES): expedited WES designed for faster turnaround in critically ill patients.

rWGSRapid whole genome sequencing (rWGS): expedited WGS for rapid diagnosis in acute clinical settings.

urWGSUltra-rapid whole genome sequencing (urWGS): shortest-turnaround WGS option used when immediate results are essential (e.g., NSIGHT2 urWGS subgroup).

Whole transcriptome sequencing (RNAseq)

DefinitionWhole transcriptome sequencing (RNAseq) sequences RNA to detect aberrant gene expression and splicing abnormalities that may explain disease when DNA sequencing is nondiagnostic.

Diagnostic contributionRNAseq can identify variants affecting splicing or expression not evident from DNA sequencing and has been shown to provide additional diagnoses in select cohorts.

Evidence statusCurrent evidence is limited and insufficient for routine clinical implementation; further studies are needed.

Whole genome optical mapping (OGM)

Technology descriptionWhole genome optical mapping (OGM) analyzes ultra-high-molecular-weight DNA to detect structural variants and chromosomal abnormalities.

Potential utilityOGM may identify SVs and complex rearrangements with higher resolution than standard cytogenetics.

Investigational statusOGM is currently investigational with proof-of-principle studies; clinical utility in routine diagnostics is not yet established.

Diagnostic WGS/WES

DefinitionDiagnostic WGS/WES refers to whole genome or whole exome sequencing performed in a clinical diagnostic setting for rare diseases, epilepsy, prenatal diagnosis and other genetic conditions.

Laboratory expectationDiagnostic WGS/WES should be performed in accredited laboratories with validated tests; research results require confirmation in a diagnostic lab before reporting.

Clinical applicationsUsed for diagnosing rare Mendelian disorders, neurodevelopmental disorders, epilepsy, and selected prenatal indications when results inform management.

genome/exome sequencing

Applications referencedGenome/exome sequencing is referenced for prenatal diagnosis and pediatric neurology (including critically ill infants) in cited literature and guidance.

Guidance linkageProfessional society guidance and cited studies discuss use of ES/GS in prenatal settings and pediatric neurology where it may improve diagnostic yield.

Evidence contextReferences include ISPD position statement and multiple clinical utility studies supporting targeted use of genome/exome sequencing.

Similarly, rapid/ultra-rapid sequencing is supported only for inpatient critically ill infants; outpatient rapid testing is considered unsupported and may be denied.

The policy lists several technologies and contexts that are not sufficiently supported for routine coverage: outpatient rapid/ultra-rapid sequencing, routine RNA sequencing (whole transcriptome sequencing), and whole genome optical mapping are considered investigational or not medically necessary based on current evidence.

Requests for these technologies for routine diagnostic purposes should be evaluated against the policy language and are likely to be considered unsupported when criteria are not met.

No additional not-covered content is provided in this fragment beyond items already summarized; the policy reiterates that coverage decisions must align with the member-specific benefit plan document and applicable mandates.

As an informational policy, it does not replace plan terms; reviewers should validate coverage against the member's benefit contract.

The policy text does not include a separate, explicit single-block list of test exclusions in the fragment beyond the previously noted unproven/not medically necessary uses; rather, it integrates those limitations into the coverage and not-covered sections (e.g., prenatal cfDNA, PGT, fetal demise evaluation, outpatient rapid sequencing, RNAseq, OGM).

Operationally, the policy treats those uses as unsupported for outpatient WES/WGS and directs providers to the criteria for covered indications where WES/WGS may be appropriate.

Providers are instructed to verify coding and any prior authorization requirements with the updated code list; the policy notes the recent code additions and recommends using current codes when requesting authorization to avoid processing errors.

Because plan terms and prior authorization workflows vary, providers should confirm code use and authorization requirements with UnitedHealthcare and reference the member-specific benefit plan document.