CurrentUnitedHealthcarePolicy CS150.U

Whole Exome and Whole Genome Sequencing (Non-Oncology Conditions) – Community Plan Medical Policy

Defines medical necessity criteria, coverage rationale, applicable clinical indications, exclusions, and applicable procedure codes for outpatient or discharge testing of WES/WGS (non-oncology) including prenatal and reanalysis criteria; excludes certain states where state-specific policies apply.

Policy Summary

PayerUnitedHealthcare

PolicyWhole Exome and Whole Genome Sequencing (Non-Oncology Conditions) – Community Plan Medical Policy

Policy CodePolicy CS150.U

Change TypeMultiple substantive updates (criteria, codes, technologies)

Effective DateApril 1, 2026

Next Review Date

Key ActionEnsure WES/WGS is ordered by an appropriate specialist and document that results will directly impact medical management and meet coverage criteria.

SourceLink

POLICY UPDATE CHANGES

Genetic counseling is strongly recommended prior to WES or WGS.

Epigenetic signature analysis is considered unproven and not medically necessary for any indication.

Replaced phrase 'proven and medically necessary when [listed] criteria are met' with 'WES/WGS, with or without concurrent Comparator Analysis, is proven and medically necessary when [listed] criteria are met.'

Removed requirement for WGS that 'neither CMA nor WES have been performed, or CMA/WES were nondiagnostic'.

Coverage criteria language revised to require that clinical presentation does not fit a Well-Delineated Genetic Syndrome and specifies that targeted testing should precede WES/WGS when a syndrome is suspected.

Prenatal WES specimen language simplified to 'specimen is obtained from amniotic fluid and/or chorionic villi or DNA is extracted from fetal blood or tissue.'

Clarified reanalysis criteria: at least 18 months since initial testing and new unexplained symptoms.

Added definitions for Autism Spectrum Disorder, Congenital Anomaly, Epileptic Encephalopathy, Targeted Panel, Well-Delineated Genetic Syndrome.

Removed content/language pertaining to the state of Louisiana; template update.

Removed definitions for Next Generation Sequencing (NGS) and Variant of Unknown Significance (VUS).

Added CPT codes 0318U, 0582U, 0583U, and 81354 to Applicable Codes.

The Description of Services, Clinical Evidence, and References sections were updated to reflect current information; previous policy version CS150.T archived.

MultipleCovered Indications (conditional)

ManyApplicable Codes listed

SeveralNot Medically Necessary Categories

48%Max reported GS diagnostic yield

36%Reported WES yield (NDD meta-analysis)

>=18 moMinimum reanalysis interval

Coverage Summary

This coverage policy (CS150.U, effective April 1, 2026) addresses outpatient and discharge use of Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS) for non‑oncology conditions. The policy stance is mixed: WES/WGS (with or without concurrent Comparator Analysis) are proven and medically necessary when specified clinical criteria are met, but several related technologies and uses (including whole transcriptome sequencing, optical genome mapping, and episignature/epigenetic signature analysis) are considered unproven and not medically necessary for routine indications. The policy defines covered indications, reanalysis and prenatal criteria, and documents provider responsibilities for ordering, counseling, and medical record documentation. Genetic counseling is emphasized as a strong recommendation prior to WES/WGS. The policy also lists applicable procedure codes (including newly added CPT/PLA codes) and notes that benefit coverage is subject to federal, state, and contractual terms.

Policy metadata and thresholds

policy_numberCS150.U

subjectWhole Exome and Whole Genome Sequencing (Non-Oncology)

statusCURRENT

effective date (dates.effective)April 1, 2026

scope_summaryDefines medical necessity criteria, coverage rationale, applicable clinical indications, exclusions, and applicable procedure codes for outpatient or discharge testing of WES/WGS (non-oncology) including prenatal and reanalysis criteria; excludes certain states with state-specific policies.

Reanalysis interval (threshold)>= 18 months since initial WES/WGS

Age limits (intellectual disability / hearing-visual impairment)Diagnosed by 18 years of age

Onset age (epileptic encephalopathy)Onset before 3 years of age

Medical-Necessity Criteria

Primary Coverage Criteria for WES/WGS (Non-Oncology Conditions)

Whole Exome Sequencing (WES) or Whole Genome Sequencing (WGS), with or without concurrent Comparator Analysis, is proven and medically necessary when ALL of the following criteria are met:

ALL of the following

The affected individual displays signs or symptoms of an undiagnosed or unexplained disorder with a suspected genetic cause.
Test results are intended to directly impact the individual's medical management.
The clinical presentation does not fit a Well-Delineated Genetic Syndrome or disorder for which a specific test or a Targeted Panel test is available. If a specific genetic syndrome is suspected, a single gene or Targeted Panel should be performed prior to determining if WES or WGS is necessary.
The test is ordered by a medical geneticist, neonatologist, neurologist, immunologist, or developmental pediatrician.

Not Medically Necessary / Unproven Indications

WES, WGS, and related technologies are unproven and not medically necessary for the following (not exhaustive):

ANY of the following

Evaluation of fetal demise
Prenatal testing via cell-free fetal DNA
Preimplantation Genetic Testing (PGT) in embryos
Screening and evaluating disorders in individuals when the above criteria are not met
Preimplantation Genetic Testing (PGT) in embryos (explicitly listed for WGS and WES)

Evidence, Reanalysis, and Specialty Guidance

Reanalysis of WES/WGS Data

Reanalysis or repeat sequencing may yield additional diagnoses under specified circumstances:

ALL of the following

Reanalysis of existing ES data at multiple time points alone may be insufficient; incorporation of additional methods (repeat sequencing, trio sequencing, microarray-based CNV detection) can increase diagnostic yield.
Studies recommend reanalysis interval of at least 18 months.
Systematic reanalysis identifies diagnoses that physician-initiated reevaluation may miss.
Schobers et al. found systematic reevaluation increased diagnostic yield by additional cases.

Rapid/Ultra-Rapid Whole Exome/Genome Sequencing (rWES/rWGS/urWGS)

Use in critically ill inpatient infants is supported; outpatient use not supported due to lack of evidence:

ANY of the following

Coding

Covered / Applicable Procedure Codes (WES/WGS and related services)mixed

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, whole genome... each comparator genome (e.g., parent, sibling).
0214U	Rare diseases, whole exome and mitochondrial DNA sequence analysis, proband.
0215U	Rare diseases, whole exome... each comparator exome (e.g., parent, sibling).
0260U	Identification of copy number variations... by optical genome mapping.
0264U	Identification of copy number variations by optical genome mapping.
0265U	Whole genome and mitochondrial DNA sequence analysis, blood, FFPE, saliva, buccal swabs or cell lines.
0266U	Tissue-specific gene expression by whole-transcriptome and NGS, reported as presence/absence of splicing or expression change.
0267U	Identification of copy number variations by optical genome mapping and whole genome sequencing.

1–10 of 27

1/3

Recently Added CPT CodesCPT

0318U
0582U
0583U
81354

Provider Actions

Documentation Required

Ordering provider specialty requirement

Ordering provider specialty requirement: WES/WGS must be ordered by an appropriate specialist to ensure clinical appropriateness and interpretation. Enter documentation showing the ordering provider's specialty (e.g., medical geneticist, neonatologist, neurologist, immunologist, developmental pediatrician, or maternal-fetal medicine specialist for prenatal cases) and their rationale for ordering WES/WGS.

Include provider name, NPI, specialty, and contact information
Attach consult note or referral from required specialist documenting clinical assessment and rationale

Documentation Required

Clinical justification

Clinical justification: Provide a concise clinical summary documenting the affected individual's signs, symptoms, and reason WES/WGS is likely to alter medical management. Populate with relevant history, prior diagnostic testing (and results), family history, and how the requested test meets policy clinical criteria.

Background

Background: WES interrogates the exome (the ~1–2% of the genome that encodes protein) and captures most known disease‑causing variants; WGS sequences all nucleotides and can detect variants across coding and noncoding regions, including copy‑number and structural variants, repeat expansions, and mitochondrial sequence changes. Evidence indicates both technologies can provide substantial diagnostic yield for many rare and neurodevelopmental disorders, and WGS may add diagnoses in some settings, though yields and utility vary by phenotype and study design.

Related and emerging assays discussed in the policy include whole transcriptome sequencing (RNAseq/TS), which characterizes RNA transcripts and can increase diagnostic yield when integrated with WES/WGS in selected, referral populations but is limited by tissue‑specific expression; optical genome mapping (OGM), a mapping technology for structural variants that shows proof‑of‑principle concordance with standard cytogenetics but requires further clinical utility validation; and epigenetic/episignature testing (DNA methylation analyses) that has shown diagnostic yield in some cohorts but is limited to disorders with known methylation biomarkers and is considered unproven for routine use by this policy.

Rationale and limitations: WES/WGS produce large numbers of variants that require specialist interpretation and often benefit from parental/comparator samples (trio testing) and periodic reanalysis as variant classification and gene‑disease knowledge evolve. Rapid and ultra‑rapid sequencing have demonstrated high diagnostic yields in critically ill inpatient infants and are reserved for those settings; evidence does not support their outpatient use. Because of interpretation complexity and implications for management, the policy strongly recommends pre‑ and post‑test genetic counseling and that appropriate specialists order and interpret testing.

Revision History

2026-04-01policy_revision_dateLatest

Policy effective date updated to April 1, 2026 (Policy revision date).

2026-04-01addedLatest

Genetic counseling is strongly recommended prior to WES or WGS.

2026-04-01removed

Policy Summary

PayerUnitedHealthcare

PolicyWhole Exome and Whole Genome Sequencing (Non-Oncology Conditions) – Community Plan Medical Policy

Policy CodePolicy CS150.U

Change TypeMultiple substantive updates (criteria, codes, technologies)

Effective DateApril 1, 2026

Next Review Date

Key ActionEnsure WES/WGS is ordered by an appropriate specialist and document that results will directly impact medical management and meet coverage criteria.

SourceLink

On This Page

Clinical presentation includes either:

ONE of
- Multiple Congenital Anomalies affecting at least two different organ systems.
- Intellectual Disability characterized as moderate, severe, or profound, diagnosed by 18 years of age.
- Global Developmental Delay.
- Epileptic Encephalopathy with onset before three years of age.
OR TWO or more of
- Congenital Anomaly.
- Significant hearing or visual impairment diagnosed by 18 years of age.
- Laboratory abnormalities suggestive of an inborn error of metabolism.
- Autism Spectrum Disorder.
- Neuropsychiatric condition (e.g., bipolar disorder, schizophrenia, obsessive-compulsive disorder).
- Hypotonia or hypertonia in infancy.
- Dystonia, ataxia, hemiplegia, neuromuscular disorder, movement disorder, or other serious neurologic abnormality.
- Unexplained developmental regression unrelated to Autism Spectrum Disorder or epilepsy.
- Growth abnormality (e.g., failure to thrive, short stature, microcephaly, macrocephaly, or overgrowth).
- Persistent and severe immunologic or hematologic disorder.
- Dysmorphic features.
- Consanguinity.
- Other first- or second-degree family member(s) with similar clinical diagnosis.

Non-concurrent Comparator Analysis

Non-concurrent Comparator Analysis for WES or WGS is proven and medically necessary when both of the following criteria are met:

ALL of the following

The affected individual meets the above criteria for WES or WGS.
WES or WGS has been previously performed on the affected individual.

Reanalysis of WES or WGS data

Reanalysis of WES or WGS data is proven and medically necessary when ALL of the following criteria are met:

ALL of the following

At least 18 months have passed since the initial WES or WGS was performed.>= 18 months
Minimum interval threshold for reanalysis.
The affected individual meets the above criteria for WES or WGS.
And either of the following occurs:
- The affected individual experiences additional symptoms after initial WES or WGS that cannot be explained by the results of the initial testing.
- New data or new family history emerges which suggests a link between the individual's symptoms and specific genes.

Prenatal WES

Prenatal WES is proven and medically necessary for diagnosing or evaluating a genetic disorder when ALL of the following criteria are met:

ALL of the following

Chromosome microarray analysis (CMA) and/or karyotyping has been performed but was uninformative.
WES is ordered by or in consultation with a medical geneticist or maternal-fetal medicine specialist (perinatologist).
The specimen is obtained from amniotic fluid and/or chorionic villi, or DNA is extracted from fetal blood or tissue.
Specimen requirements must be met for prenatal testing.
The fetus has one or more of the following:
- Multiple Congenital Anomalies affecting at least two different organ systems.
- Fetal hydrops of unknown etiology.
- A Congenital Anomaly affecting a single organ system and family history that suggests a genetic etiology.

Prenatal genetic diagnosis or screening (for WGS)

Use of rapid WES (rWES), rapid WGS (rWGS), or ultra-rapid WGS (urWGS) in outpatient settings

Whole transcriptome sequencing, epigenetic signature analysis, and optical genome mapping (OGM) for any indication

rWES/rWGS/urWGS demonstrate high diagnostic yield in critically ill infants (pooled diagnostic yield ~42%; individual studies report 19–50% depending on modality).
Evidence supports inpatient critically ill use; not supported in outpatient setting.
urWGS may provide faster turnaround and higher diagnostic rate in severe cases and can be valuable when immediate clinical intervention is required.
Kingsmore et al.: urWGS diagnostic rate 46% vs ~19-20% for rWES/rWGS.

Whole Transcriptome Sequencing (RNAseq/TS)

Currently insufficient evidence for routine diagnostic use; may be considered as adjunct in select unresolved cases:

ANY of the following

RNAseq can increase diagnostic yield when integrated with WES/WGS in selected referral populations (e.g., Lee et al.: 15% additional diagnoses among WGS-negative probands).
Limited by tissue-specific expression and specialist center experience.
Combined GS and TS may be useful as second-tier testing in complex immunodeficiency cases where standard testing is nondiagnostic.
Rozevska et al. found TS instrumental for characterizing complex structural variants but overall limited improvement over exome sequencing.

Optical Genome Mapping (OGM)

Insufficient evidence for clinical use at this time:

ALL of the following

OGM shows proof-of-principle concordance with standard assays for many chromosomal abnormalities but requires further development and clinical utility studies.
Mantere et al. reported 100% concordance across certain abnormalities in a proof-of-principle study.

Epigenetic Signature Analysis (Episignature/DNA methylation testing)

Insufficient evidence for routine diagnostic use but may provide diagnostic yield in unresolved rare disorders:

ANY of the following

Clinical DNA methylation episignature testing demonstrated diagnostic yields (e.g., 18.7% in comprehensive analysis cohort; 32.4% in targeted VUS/suspected cases) and may reclassify cases.
Limitations include restriction to conditions with known biomarkers and potential false positives from overlapping episignatures.

Professional Society Recommendations (selected)

Guidance summarized from multiple organizations regarding WES/WGS utilization:

ANY of the following

ACMG: Recommends WES/WGS as first- or second-tier for congenital anomalies, developmental delay, or intellectual disability with onset in childhood; supports reanalysis policies.
Also provides 'points to consider' on SV detection and prenatal contexts.
AAP: Recommends CMA and WES (sequential or concurrent) as first-tier in GDD/ID; reanalysis every 1–2 years if negative.
NICE/ILAE/NSGC: Recommend WES/WGS (often as first-line) for many unexplained epilepsies and specific age/phenotype criteria; emphasize qualified provider and genetic counseling.
NICE recommends considering WGS for epilepsy with onset <2 years, or 2-3 years if specialist recommends.
ACOG/ISPD: Do not recommend routine prenatal WES/WGS outside specialty contexts; consider when fetal anomalies are present and prior CMA/karyotype are negative or in specific recurrent/complex scenarios.
ASHG/AANEM: Support targeted or broader testing depending on presentation; WES/WGS appropriate when prior targeted testing fails or in selected initial testing scenarios.

Key definitions for clinical use include: Comparator Analysis — genetic testing of close relatives (typically trio testing) to aid interpretation; Well‑Delineated Genetic Syndrome — a recognizable syndrome with specific traits for which targeted or single‑gene testing may be appropriate; Whole Exome Sequencing (WES) — sequencing of all exons (protein‑coding regions); Whole Genome Sequencing (WGS) — sequencing of the full genome including coding and noncoding regions; Trio sequencing — sequencing the proband plus both biological parents; rWES/rWGS/urWGS — rapid and ultra‑rapid sequencing with shortened turnaround for critically ill patients; and Episignature testing — DNA methylation‑based clinical testing for disease‑specific methylation patterns used in selected rare disorders.

Study	Finding
Albuquerque et al. (2025)	GS-specific diagnostic yield 7.0% after negative ES; ES reanalysis diagnostic rate 14.2%; total GS yield 24.1% in subset.
Pandey et al. (2025)	Pooled diagnostic yield 34.2% for GS or ES vs 18.1% for non‑GWS; pooled clinical utility ~58.7% for GS and 54.5% for ES among positives.
Chung et al. (2023) meta-analysis	Overall diagnostic yields similar for ES (38%) and GS (34%); GS showed higher pooled clinical utility in some analyses.
Sheidley et al. (2022) pooled epilepsy studies	Pooled diagnostic yields: GS 48%; ES 24%; multi‑gene panels 19%; CMA/CGH 9% across epilepsy studies.
Xiao et al. (2022) rapid sequencing meta‑analysis	Pooled diagnostic yield for rapid sequencing in critically ill infants 42% (rWES 50%, rWGS 37%).
Kingsmore et al. (2019) NSIGHT2 RCT	urWGS diagnostic rate 46%; rWES/rWGS ~19–20%; urWGS faster turnaround and higher yield in severely ill infants.
Schobers et al. (2022)	Systematic re‑evaluation (resequencing/reanalysis) increased total diagnostic yield to 53% among 103 children; systematic reanalysis identified diagnoses physician‑initiated review missed.
Vorsteveld et al. (2024)	Initial ES diagnostic yield 11.8%; systematic reanalysis increased overall yield to 15.2% (median reanalysis interval 47.5 months).
Tan et al. (2020) reanalysis review	Incorporating repeat sequencing, trio testing, and CNV detection increased diagnostic yield; recommended reanalysis interval ≥18 months.
Lee et al. (2020) RNAseq adjunct	RNAseq added 7 diagnoses (15%) among 48 families with negative WGS, increasing overall yield to 38% in that cohort.
Mantere et al. (2021) OGM proof‑of‑principle	OGM showed 100% concordance with standard assays across 99 chromosomal abnormalities in a proof‑of‑principle study; further clinical utility studies needed.
Kerkhof et al. (2024) episignature testing	Clinical DNA methylation episignature testing diagnostic yields: 18.7% in comprehensive cohort; 32.4% in targeted VUS/suspected cases; confirmation rates varied.
Sotiriadis et al. (2025)	Pooled incremental prenatal ES yield in unselected structurally normal fetuses after normal CMA/karyotype was low (~1.6%); most benefits in selected cases.
Mellis et al. (2022) prenatal ES meta‑analysis	Pooled incremental diagnostic yield of prenatal ES over CMA/karyotype 31% (range 2%–53% by phenotype).
Jiang et al. (2025) prenatal skeletal abnormalities	ES additional detection rate over standard testing 63.2% for fetal skeletal abnormalities (subgroup rates up to ~85%).
Blayney et al. (2024)	Pooled incremental prenatal ES yield for CNS anomalies 32% overall; higher with multisystem involvement.

Summary of presenting problems and timeline of symptom onset
Relevant physical findings, developmental assessments, and specialty evaluations
Prior genetic and non-genetic testing performed (e.g., CMA, karyotype, targeted gene/panel testing) with dates and results
Specific ways test results are expected to impact immediate medical management or decision-making

Documentation Required

Prenatal specimen and consultation requirements

Prenatal specimen and consultation requirements: For prenatal WES, document that chromosome microarray and/or karyotype were uninformative, and that testing was ordered by or in consultation with a medical geneticist or maternal-fetal medicine specialist. Specify specimen source and collection details.

Documentation of prior CMA and/or karyotype testing and results
Consultation note or order from medical geneticist or maternal-fetal medicine specialist
Specimen source: amniotic fluid, chorionic villi, or fetal blood/tissue; include collection date and method
Indication: fetal ultrasound/clinical findings (e.g., multiple congenital anomalies, fetal hydrops, single-organ anomaly with suggestive family history)

Documentation Required

Reanalysis timing and trigger documentation

Reanalysis timing and trigger documentation: Document dates of original WES/WGS and justify reanalysis timing per policy. Reanalysis is considered when at least 18 months have elapsed and new clinical information or family data suggest a genetic etiology.

Date of initial WES/WGS and copy of original report
Statement that >= 18 months have passed since initial testing
Description of new or progressive clinical features, new family history, or new literature that prompted reanalysis
Clear statement of how reanalysis could change diagnosis or management

Documentation Required

Consideration of evidence when ordering WES/WGS

Consideration of evidence when ordering WES/WGS: Document why WES/WGS is preferred over single-gene or targeted panel testing for this presentation, including that the presentation does not fit a well-delineated genetic syndrome and that targeted testing is not expected to be diagnostic.

Rationale that clinical features are nonspecific or involve multiple systems making panel testing less likely to be diagnostic
Documentation that a targeted single-gene or panel test is not indicated or has been previously performed and was non-diagnostic
Explanation of how results will be used for medical management

Documentation Required

Reanalysis recommendations

Reanalysis recommendations: When reanalysis is appropriate, document the reason and requested scope (e.g., updated variant interpretation, new gene-disease associations). Indicate whether comparator (trio) analysis or additional family testing is requested to aid interpretation.

Specify reanalysis scope: bioinformatic pipeline updates, variant reinterpretation, updated gene lists
Include any new family member samples requested for comparator analysis
Attach any new clinical data or publications supporting re-evaluation

Documentation Required

Consider reanalysis and additional testing

Consider reanalysis and additional testing: If initial WES/WGS is non-diagnostic, document consideration of reanalysis and additional targeted testing (including non-sequencing assays) when clinically indicated. Provide justification for additional tests and their expected contribution.

Rationale for additional testing (e.g., repeat sequencing, mitochondrial testing, biochemical studies, functional assays)
Clinical questions to be addressed by additional tests and how results will change management
Plan for timing of reanalysis or further testing

Documentation Required

Use qualified personnel and genetic counseling

Use qualified personnel and genetic counseling: Document that testing was ordered or reviewed by qualified personnel and that genetic counseling was provided or offered. Strongly recommend pre-test counseling to discuss benefits, limitations, possible incidental findings, and implications for family members.

Name and qualifications of personnel interpreting or ordering the test (e.g., board-certified geneticist, certified genetic counselor)
Evidence of pre-test counseling: date, counselor name, topics discussed, informed consent documentation
Plan for post-test counseling to communicate results and implications to the family

Documentation Required

Prenatal sequencing considerations

Prenatal sequencing considerations: For prenatal WES/WGS, include documentation of the fetal imaging findings, the urgency and anticipated impact on pregnancy management, and counseling provided to the family on limitations of prenatal sequencing.

Fetal ultrasound/MRI findings and dates
Discussion of potential outcomes, limitations of prenatal sequencing, and implications for pregnancy care
Confirmation that specimen source is appropriate and adequate for testing

Documentation Required

Medical records required for review

Medical records required for review: Supply complete and legible medical records to support medical necessity determinations, including consult notes, prior test results, imaging reports, and family history documentation.

Relevant specialty consult notes (genetics, neurology, neonatology, MFM, etc.)
Results of prior genetic tests (CMA, karyotype, targeted panels), laboratory and imaging reports
Detailed family pedigree or family history documentation

Documentation Required

Refer to federal/state/contractual benefit terms

Refer to federal/state/contractual benefit terms: Coverage is subject to applicable federal, state, and contractual requirements. Document any state-specific mandates or contract terms that may affect coverage and include those references in the prior authorization submission when relevant.

Note if the request is for a state with a state-specific policy (see policy Application section)
Attach relevant benefit plan language or state mandate documentation if applicable

Documentation Required

Use policy in conjunction with clinical judgment and tools

Use policy in conjunction with clinical judgment and tools: This policy is a framework; document how clinical judgment, specialty consultation, and available decision-support tools were applied to the patient's case when ordering WES/WGS.

Note any decision support tools or algorithms consulted (e.g., specialty society guidance)
Brief explanation of how clinical judgment influenced the decision to order WES/WGS

Prior Authorization

Rapid sequencing reserved for critically ill inpatients

Rapid sequencing reserved for critically ill inpatients: Rapid/ultrarapid WES/WGS is generally reserved for critically ill newborns or infants currently admitted to an inpatient setting where results would meaningfully and immediately alter clinical care. Outpatient rapid sequencing is not supported by this policy.

Rapid sequencing appropriate only for critically ill inpatients (e.g., NICU/PICU) with potential immediate management impact
Outpatient rapid sequencing requests are not supported per policy

Billing Rule

Updated applicable codes list

Updated applicable codes list: Report or add the following CPT codes as applicable when billing for services described in this policy. Ensure coding matches the services performed and documentation supports the codes reported.

0318U
0582U
0583U
81354

Documentation Required

Genetic counseling recommendation

Genetic counseling recommendation: Pre-test genetic counseling is strongly recommended for all individuals (or their guardians) undergoing WES/WGS to discuss potential results, limitations, incidental findings, and familial implications. Document counseling in the medical record.

Document date and provider of counseling, topics discussed, and informed consent for testing
Confirm plan for post-test counseling to disclose results and recommendations

Epigenetic signature analysis removed from covered technologies; considered unproven and not medically necessary for any indication.

2026-04-01revisedLatest

Wording clarified to specify 'WES/WGS, with or without concurrent Comparator Analysis, is proven and medically necessary when [listed] criteria are met.'

2026-04-01removedLatest

Removed requirement that WGS be contingent on prior CMA/WES not having been performed or being nondiagnostic.

2026-04-01revisedLatest

Coverage criteria revised to clarify that when a Well-Delineated Genetic Syndrome is suspected, targeted single-gene or Targeted Panel testing should be performed prior to WES/WGS; sequencing order clarified.

2026-04-01revisedLatest

Prenatal WES specimen language simplified: specimen is obtained from amniotic fluid and/or chorionic villi or DNA is extracted from fetal blood or tissue (removed reference to cultured cells).

2026-04-01addedLatest

Clarified reanalysis criteria: at least 18 months have passed since initial testing and new unexplained symptoms or new data/family history justify reanalysis.

2026-04-01added

New definitions added for Autism Spectrum Disorder, Congenital Anomaly, Epileptic Encephalopathy, Targeted Panel, and Well-Delineated Genetic Syndrome.

2026-04-01removed

Removed multiple prior definitions including Next Generation Sequencing (NGS) and Variant of Unknown Significance (VUS) (definition removals reflected in revision history).

2026-04-01administrative

Administrative/template update: removed content/language pertaining to the state of Louisiana; archived prior policy version CS150.T.

2026-04-01addedLatest

Applicable Codes updated: added CPT/PLA codes 0318U, 0582U, 0583U, and 81354 to Applicable Codes.

2026-04-01revised

Supporting sections (Description of Services, Clinical Evidence, References) updated to reflect current information.