CurrentUnitedHealthcarePolicy CS150ID.A

Whole Exome and Whole Genome Sequencing (Non-Oncology Conditions) (for Idaho Only)

Defines medical necessity criteria, limitations, and not-medically-necessary indications for Whole Exome Sequencing (WES), Whole Genome Sequencing (WGS), prenatal WES, rapid sequencing modalities, whole transcriptome sequencing, and whole genome optical mapping for non-oncology conditions for Idaho members (including Idaho Medicaid Plus).

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS150ID.A

Change TypeAdministrative updatesnew policy

Effective DateJun 1, 2025

Next Review Date

Key ActionOrder WES/WGS only when criteria are met and document that results are expected to directly influence medical management, with testing ordered by a qualified specialist and genetic counseling provided.

SourceLink

POLICY UPDATE CHANGES

08/01/2025, Updated reference link to reflect the current policy title for FDA Cleared or Approved Companion Diagnostic Testing (for Idaho Only).

06/01/2025, New Medical Policy

MultipleCovered Indications (conditional)

SeveralProcedure Codes Referenced

>=18moReanalysis Interval

36%

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Pooled ES yield (NDD)

53%ES yield (NDD with assoc. conditions)

31%Incremental prenatal ES yield over CMA/karyotype

Coverage Summary

Whole Exome Sequencing (WES) analyzes the protein-coding regions of the genome (the exome), which represent approximately 1–2% of the genome and contain most known disease-causing variants; Whole Genome Sequencing (WGS) determines the sequence of the entire genome including coding and noncoding regions and can detect additional variant types such as copy number variants (CNVs), structural variants (SVs), repeat expansions, and nonexonic regulatory or splicing variants.

This policy applies to Idaho members (including Idaho Medicaid Plus) and defines the scope of coverage for WES and WGS in non-oncology conditions: both tests are covered conditionally when specified medical necessity criteria are met (for example, when results are expected to directly influence medical management and the clinical presentation is nonspecific), and several indications and limitations (including prenatal, comparator testing, reanalysis, and restrictions on rapid sequencing in outpatient settings) are detailed in the policy.

Genetic counseling is strongly recommended prior to WES or WGS to inform individuals about advantages and limitations of testing. Coverage stance for these technologies is stated as mixed. This policy is effective June 1, 2025.

Key thresholds and quick facts

Policy numberCS150ID.A

SubjectWhole Exome and Whole Genome Sequencing (Non-Oncology) for Idaho

Reanalysis interval (policy threshold)>= 18 months

Suggested reanalysis interval (literature)2-3 years (suggested by Wenger et al.)

Age cutoff for ID / sensory impairment diagnoses<= 18 years

Onset cutoff for epileptic encephalopathy< 3 years

Medical-Necessity Criteria

Not Medically Necessary / Unproven

Evidence and Professional Society Recommendations

Evidence	Summary/Value
Meta-analysis diagnostic rate
ES 38% (95% CI 36-40%), GS 34% (95% CI 30-38%) overall (Chung et al. 2023)
Clinical utility pooled
GS 61% (95% CI 50-73%), ES 48% (95% CI 40-56%) (Chung et al. 2023)
ES diagnostic yield for short stature
27.1% (95% CI 18.1-37.2%) vs CMA 13.6% (95% CI 9.2-18.7%) (Li et al. 2023)
WES diagnostic rate for intellectual disability
42% (95% CI 35-50%) (Sánchez-Luquez et al. 2022)
Infant ICU randomized trial (WGS)
Early WGS doubled change in management and molecular diagnosis at 60 days vs delayed (Krantz et al. 2021)
Large WGS cohort (Turro 2020)
WGS in 13,037 participants; identified 95 Mendelian associations; genetic diagnosis in 1,138 of 7,065 extensively phenotyped.
Srivastava meta-analysis
ES yield 36% overall (31% isolated NDD, 53% NDD with associated conditions); recommends ES as first-tier for unexplained NDDs.
Clark et al. (2018) meta-analysis
WES/WGS diagnostic utility greater than CMA; WGS clinical utility greater than CMA (p < 0.0001).
Incremental yield of ES over CMA/karyotyping
Pooled incremental diagnostic yield of ES over CMA/karyotyping = 31% (95% CI 26%-36%) (Mellis et al. 2022)
Reanalysis outcomes
Reanalysis or resequencing yields additional diagnoses 15%-53% depending on method; median time to reanalysis ~22 months; recommendations for reanalysis at ~18 months (Bullich, Schobers, Nambot, Tan)
RNAseq and OGM findings
RNAseq added diagnoses in selected cohort: 15% (Lee et al. 2020); OGM proof-of-principle showed 100% concordance for evaluated anomalies in small study (Mantere et al. 2021)

Coding

Listed Procedure Codes (reference only)mixed

0094U	Genome (e.g., unexplained constitutional or heritable disorder or syndrome), rapid sequence analysis.
0212U	Whole genome and mitochondrial DNA sequence analysis, proband (rare diseases).
0213U	Whole genome and mitochondrial DNA sequence analysis, each comparator genome.
0214U	Whole exome and mitochondrial DNA sequence analysis, proband.
0215U	Whole exome and mitochondrial DNA sequence analysis, each comparator exome.
0260U	Identification of structural variants by optical genome mapping.
0264U	Identification of structural variants by optical genome mapping.
0265U	Whole genome and mitochondrial DNA sequence analysis, various specimen types.
0266U	Tissue-specific gene expression by whole-transcriptome sequencing.
0267U	OGM and WGS structural variant identification.

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Provider Actions & Billing Guidance

Documentation Required

Ordering clinician specialty requirement

WES or WGS must be ordered by an appropriate specialist to ensure proper test selection, interpretation, and follow-up care are available.

Documentation Required

Clinical justification

Clinical justification for WES/WGS must document how results are expected to directly influence medical management or clinical outcomes. Include specific examples of the anticipated change in care (e.g., a change in medication, surgical plan, surveillance strategy, or referral to a specialist).

Document expected influence on management (e.g., treatment change, surveillance, referral).

Documentation Required

Document prior diagnostic testing for prenatal WES

For prenatal WES, include documentation of prior diagnostic testing that was uninformative before ordering WES.

Definitions

Term	Definition
Comparator
A DNA sequence used to compare to the individual's DNA sequence (e.g., parent or sibling).
Consanguinity
Procreation with second-cousins or closer.
Global Developmental Delay
Significant delay in 2 or more developmental domains with onset prior to 5 years of age.
Intellectual Disability
Condition diagnosed before age 18 including below-average intellectual function and lack of daily living skills.
Next Generation Sequencing (NGS)
Sequencing techniques that analyze multiple sections of DNA simultaneously.
Preimplantation Genetic Testing (PGT)
Testing of oocytes or embryos for HLA-typing or genetic abnormalities (PGT-A, PGT-M, PGT-SR).
Variant of Unknown Significance (VUS)
A genetic variation with unknown association with disease.
Whole Exome Sequencing (WES)
Sequencing of the exons (protein-coding regions) of the genome (~1-2% of genome).
Whole Genome Sequencing (WGS)
Sequencing of the entire genome including coding and non-coding regions; can detect CNVs, SVs, repeat expansions, and nonexonic variants.
Diagnostic yield
Proportion of tested individuals with pathogenic or likely pathogenic variants that explain the phenotype.
Trio testing
Sequencing of proband and both biological parents to aid interpretation and increase diagnostic yield.
Reanalysis
Periodic re-evaluation of prior sequencing data using updated bioinformatics, literature, and gene–disease associations to identify previously unrecognized diagnoses; suggested interval >=18 months (Wenger et al. suggests 2-3 years).
rWES
Rapid whole exome sequencing — expedited exome sequencing with shortened turnaround time for critically ill patients.
rWGS
Rapid whole genome sequencing — expedited whole genome sequencing for rapid diagnosis.
urWGS
Ultra-rapid whole genome sequencing — very fast WGS used for gravely ill infants requiring fastest possible turnaround.

Revision History

06/01/2025added

New Medical Policy (policy creation date recorded). Details: Policy effective date June 1, 2025; policy number CS150ID.A; establishes coverage criteria for Whole Exome and Whole Genome Sequencing (Non-Oncology Conditions) for Idaho members, including requirements for ordering clinicians, covered indications, and documentation expectations. Marked non-material per brief: no clinical policy statement changes indicated in this entry.

08/01/2025revisedLatest

Administrative update to related policy link. Details: Updated reference link to reflect the current policy title for FDA Cleared or Approved Companion Diagnostic Testing (for Idaho Only); classified as administrative with no clinical policy statement changes (non-material).

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS150ID.A

Change TypeAdministrative updatesnew policy

Effective DateJun 1, 2025

Next Review Date

SourceLink

On This Page

Billing Rule

Comparator testing

Comparator testing (e.g., parental or sibling samples) should be billed separately when performed. Ensure appropriate coding for comparator analyses.

Affected codes: 81416, 81426, 0213U, 0215U, 0336U

Denial Risk

Outpatient rapid sequencing not covered

Rapid or ultra-rapid sequencing performed in outpatient settings is not covered and may result in claim denial.

Affected codes: 0094U, 0426U
Risk: May be denied if billed for outpatient or non-eligible settings

Prior Authorization

Rapid/Ultra-rapid sequencing restricted to inpatient critically ill infants

Rapid and ultra-rapid sequencing approvals are restricted to inpatient settings for critically ill infants; outpatient requests are not supported by this policy.

Documentation Required

Consider reanalysis of negative results

Consider reanalysis of negative WES/WGS results, particularly when new symptoms, family history, or gene-disease associations emerge.

Suggested reanalysis interval: >= 18 months

Documentation Required

Genetic counseling and specialist involvement

Genetic counseling should be provided and relevant specialists involved for test selection, result interpretation, and coordination of follow-up care.

Documentation Required

Reference federal/state/contractual requirements

Follow any applicable federal, state, or contractual requirements that may affect coverage, testing, or reporting.

Documentation Required

Use independent medical judgment and tools

Providers should use their independent medical judgment and may use third-party tools or laboratories as appropriate when selecting tests and interpreting results. Document rationale for decisions in the medical record.

Documentation Required

Consider trio testing where available

When available, trio testing (proband plus both biological parents) is preferred as it increases diagnostic yield and aids interpretation.

Documentation Required

Consider reanalysis before WGS

Before ordering WGS, consider reanalysis of prior WES data if available, as reanalysis may identify diagnoses without need for WGS.

Documentation Required

Laboratory accreditation and validation

Ensure laboratories performing WES/WGS are appropriately accredited and validated for clinical testing. Maintain documentation of laboratory credentials and validation in the record.

Documentation Required

Use of sequencing as first-tier in select indications

Use of sequencing as a first-tier test is appropriate for select indications when clinical features meet the policy criteria (for example, nonspecific presentations with high likelihood of a monogenic disorder such as multiple congenital anomalies, severe intellectual disability, global developmental delay, or early-onset epileptic encephalopathy) and when results are expected to directly influence management.