Summary & Overview

CPT 0567U: Whole-Genome Sequencing with Methylation and Mitochondrial Analysis

CPT code 0567U designates the Genomic Unity® 2.0 proprietary laboratory test from Variantyx Inc., a combined short- and long-read whole–genome sequencing assay that also assesses mitochondrial abnormalities and selected regional methylation. As a PLA code, 0567U is tied to a single manufacturer's test and carries implications for coverage, billing specificity, and clinical adoption nationwide. Key national payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare.

Readers will find a concise briefing on what the code represents clinically, the types of specimens supported, and the typical service settings. The publication provides benchmarks for payer coverage and reimbursement trends, notes relevant policy updates affecting proprietary genomic tests, and outlines the clinical contexts in which whole–genome sequencing with methylation analysis is used (diagnostic evaluation of genetic and mitochondrial disorders, prenatal diagnostics, and complex undiagnosed conditions). Where input data is incomplete, the report flags missing items rather than inferring specifics. The content is intended for clinicians, coding professionals, and policy analysts seeking a national-level summary of the CPT 0567U test and its billing context.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0567UCPTProprietary Laboratory AnalysisWhole-Genome SequencingGenomic DiagnosticsMethylation AnalysisMitochondrial TestingVariantyxLaboratory Billing

Billing Code Overview

CPT code 0567U is a Proprietary Laboratory Analyses (PLA) code specific to a single test: Genomic Unity® 2.0 from Variantyx Inc. This test performs whole–genome sequencing using both short and long reads to detect a broad range of genetic and mitochondrial variants and to assess methylation status in selected regions. The assay accepts specimens from blood, saliva, amniocentesis, chorionic villus sampling, or tissue.

Service type: Advanced genomic diagnostic testing using combined short- and long-read whole-genome sequencing with targeted methylation assessment

Typical site of service: Clinical molecular diagnostics laboratories and reference genetic testing laboratories; specimens collected in outpatient clinics, inpatient settings, prenatal sampling procedures, or at specimen collection centers

Clinical & Coding Specifications

Clinical Context

A typical patient undergoing 0567U is an individual referred for comprehensive genomic analysis when standard testing has not explained a suspected genetic condition or when a broad, high-resolution assessment is clinically indicated. Examples include: a neonate with multiple congenital anomalies and unclear etiology after chromosomal microarray and targeted gene panels; an adult with complex neurodevelopmental or neurodegenerative features and prior negative exome testing; a prenatal case with abnormal ultrasound findings where parents consent to detailed genomic and methylation analysis from amniocentesis or chorionic villus sampling; or evaluation of mitochondrial disorders where both nuclear and mitochondrial genomes require assessment.

Clinical workflow:

A clinician (clinical geneticist, maternal-fetal medicine specialist, neurologist, or genetic counselor) documents medical necessity and obtains informed consent covering whole-genome sequencing and potential secondary findings.
Appropriate specimen is collected (blood, saliva, amniotic fluid, chorionic villus sample, or tissue) and sent to the laboratory performing Genomic Unity® 2.0 (Variantyx Inc.).
The laboratory performs whole-genome sequencing using combined short- and long-read technologies, analyzes mitochondrial DNA, evaluates methylation at selected regions, and interprets structural variants, copy-number variants, single-nucleotide variants, repeat expansions, and methylation signatures.
Results are returned to the ordering clinician with a clinical report that includes pathogenic/likely pathogenic findings, variants of uncertain significance as applicable, technical limitations, and recommended follow-up (e.g., confirmatory testing, cascade testing, or genetic counseling).
Billing for the proprietary PLA test uses 0567U. Common clinical sites include hospital-based genetics clinics, outpatient genetics or neurology clinics, maternal-fetal medicine units, and reference laboratories processing externally collected specimens.

Coding Specifications

Modifier	Description	When to Use
`00`	No modifier — default reporting	Use as the primary submission for the service without additional circumstances.
`22`	Increased procedural services	Use when documentation supports substantially greater laboratory effort or interpretation beyond typical service complexity.
`52`	Reduced services	Use when only a portion of the test was performed or when testing was partially completed and a reduced service was provided.
`53`	Discontinued procedure	Use when testing was started but discontinued for patient-related or technical reasons and cannot be completed.
`59`	Distinct procedural service	Use when an unrelated diagnostic service is performed on the same date and must be reported separately.
`76`	Repeat procedure by same provider	Use when the same laboratory repeats the genomic test due to sample failure or need for confirmatory run.
`77`	Repeat procedure by another provider	Use when a second lab repeats testing already performed by another lab, typically for confirmatory or referral purposes.
`RT`	Right side (anatomic) — rarely applicable	Rarely applicable; used only if specimen laterality is relevant and required by payer policies.
`LT`	Left side (anatomic) — rarely applicable	Rarely applicable; used only if specimen laterality is relevant and required by payer policies.
`91`	Repeat clinical diagnostic laboratory test	Use when the test is repeated on a subsequent specimen to confirm an unexpected result or for quality control purposes.

Taxonomy Code	Specialty	Notes
207RG0300X	Clinical Genetics	Clinical geneticists ordering and interpreting complex genomic testing.
2080P0208X	Obstetrics & Gynecology, Maternal-Fetal Medicine	Maternal-fetal medicine specialists ordering prenatal whole-genome analysis for abnormal ultrasound findings.
2084N0400X	Neurology	Neurologists managing neurodevelopmental or neurodegenerative disorders that require broad genomic evaluation.
363L00000X	Laboratory — Molecular Genetics	Reference laboratory specialty performing high-complexity genomic testing.
208D00000X	Pediatrics	Pediatricians in genetics clinics coordinating testing for congenital or developmental disorders.

ICD-10 Code	Description	Clinical Relevance
`Q87.8`	Other specified congenital malformation syndromes affecting multiple systems	Patients with multiple congenital anomalies often require broad genomic analysis to identify underlying genetic syndromes.
`R62.0`	Delayed milestone in childhood	Developmental delay frequently prompts comprehensive genomic testing when etiology is unclear after initial evaluation.
`G31.9`	Neurodegenerative disease, unspecified	Complex neurodegenerative presentations may need whole-genome testing to detect rare or atypical genetic causes.
`H35.59`	Other retinal disorders	Suspected inherited retinal dystrophies may benefit from genome-wide testing when targeted panels are non-diagnostic.
`O35.8XX0`	Maternal care for other suspected fetal conditions, unspecified fetus, first trimester	Prenatal cases with suspected fetal genetic conditions on imaging can be evaluated using comprehensive genome and methylation testing.

CPT Code	Description	Relationship to This Procedure
`81420`	Targeted genomic sequence analysis panel (e.g., 5–50 genes)	May be performed prior to `0567U` when a focused panel is indicated; negative panel results can lead to reflex to whole-genome sequencing.
`81425`	Whole exome sequencing (WES), proband only	Alternative comprehensive testing option; WES may be performed when only coding regions are required, while `0567U` provides broader genome and methylation analysis.
`81479`	Unlisted molecular pathology procedure	Used for reporting molecular tests not represented by specific CPT codes when prior authorization or additional billing guidance is required in conjunction with proprietary PLA codes.
`88172`	Cytogenetic analysis, FISH interpretation, quantitative	May be ordered alongside when structural chromosomal abnormalities need targeted validation of findings suggested by whole-genome sequencing.
`81229`	Mitochondrial DNA sequencing, complete	May be ordered separately if a payer requires a specific mitochondrial sequencing code in addition to or instead of components of the PLA test, though `0567U` includes mitochondrial analysis.

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