CPT 81349 Low‑Pass WGS Reimbursement & Policy

CPT code 81349 covers low‑pass whole genome sequencing (WGS) performed with next‑generation sequencing technology to assess the entire genome for copy‑number variants and extended runs of homozygosity. This genomic laboratory test is increasingly used in the evaluation of unexplained developmental delays, congenital anomalies, and suspected genetic disorders where detection of genome‑wide CNVs or large homozygous regions can provide diagnostic insight. Nationally, CPT code 81349 matters because it reflects a shift from microarray‑based genomic testing to sequencing‑based approaches that can offer broader genomic coverage and integration with other sequencing analyses.

Key payers in typical coverage discussions include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. The publication presents what readers need to know about clinical context, payer coverage considerations, coding practice, and benchmarks where available. It summarizes how the test is defined, typical clinical indications, and the typical laboratory and site‑of‑service settings for ordering and performing the assay.

Readers will learn: the clinical purpose and technical basis of the test; how CPT code 81349 differs from older microarray methods; common billing and coding considerations tied to laboratory sequencing services; and where to find further policy or payer‑specific guidance. Data not available in the input where payer‑specific policies, taxonomies, and associated diagnosis codes would normally be summarized.

Billing Code Overview

CPT code 81349 describes a laboratory test using low–pass whole genome sequencing performed with high‑throughput next‑generation sequencing (NGS) technology. The method evaluates the entire genome to detect copy‑number variants (CNVs) and long runs of homozygosity that may be associated with developmental delays or genetic disabilities.

Service type: Laboratory diagnostic test — genomic sequencing (low‑pass whole genome sequencing)

Typical site of service: Clinical laboratory or reference genomic testing laboratory; specimen collection may occur in outpatient clinics or inpatient settings

Data not available in the input.

Clinical Context

A 3-year-old child with global developmental delay and multiple congenital anomalies is referred by a pediatric geneticist for genomic evaluation after prior targeted testing (chromosomal microarray and fragile X testing) was unrevealing. The clinical workflow begins with the geneticist obtaining informed consent and ordering the test 81349 (low-pass whole genome sequencing for copy-number and runs of homozygosity analysis). A blood sample is collected in the outpatient phlebotomy lab or at a pediatric infusion center when venipuncture is performed under sedation for associated procedures. The specimen is shipped to a molecular genetics laboratory accredited for high-throughput next-generation sequencing. The laboratory performs DNA extraction, library preparation, low-pass whole genome sequencing, bioinformatic CNV and homozygosity calling, and technical validation. A molecular pathologist reviews results and issues a signed report with interpretation and recommendations for follow-up confirmatory testing if needed. The ordering clinician incorporates results into the patient's record and discusses findings with the family in a follow-up clinic visit, which may prompt cascade testing, referrals (e.g., neurology, developmental pediatrics), or changes in medical management.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	When billing only the professional interpretation component, if separated from the technical lab component ().

Taxonomy Code	Specialty	Notes
`2080P0208X`	Molecular Pathology	Laboratory specialists who review and interpret genomic sequencing results.
`208000000X`	Clinical Laboratory	Clinical laboratory professionals performing NGS testing and technical analysis.
`2084P0800X`	Geneticist (Clinical)	Medical geneticists who order testing and integrate results into clinical care.
`208D00000X`	Pediatrician	Pediatric specialists who commonly refer patients for genomic testing for developmental delay.
`2085R0202X`	Pathology-Anatomic & Clinical	Pathologists involved in laboratory oversight and report sign-out.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`F82`	Specific developmental disorder of motor function	Developmental delays prompting genomic CNV and homozygosity analysis.
`F80.9`	Developmental disorder of speech and language, unspecified	Speech delay commonly part of presentations evaluated with genomic testing.
`R62.0`	Delayed milestone in childhood	General developmental delay indication for genome-wide CNV testing.
`Q87.8`	Other specified congenital malformation syndromes affecting multiple systems	Multiple congenital anomalies that raise suspicion for genomic disorders detected by CNV analysis.
`G40.909`	Epilepsy, unspecified, not intractable, without status epilepticus	Seizure disorders often investigated with genomic testing for underlying copy-number variants or homozygosity regions.
`Z13.79`	Encounter for screening for other disorder	Screening encounters when family history or newborn screening prompts genomic evaluation.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81415`	Exome sequencing, clinical test, sequence analysis and interpretation (eg, exome)	Alternative comprehensive genomic test that may be ordered when sequence-level variant detection is required in addition to CNV analysis; sometimes ordered concurrently or sequentially.
`81229`	Chromosomal microarray analysis (CMA), single nucleotide polymorphism (SNP) array or comparative genomic hybridization (CGH) microarray	Traditional first-line test for copy-number variants; may be performed before or instead of low-pass WGS depending on clinical algorithm.
`81162`	Whole exome sequencing (trio) interpretation and reporting	Used when trio-based exome analysis is performed; may be part of the diagnostic workflow when broader sequence analysis is indicated.
`81479`	Unlisted molecular pathology procedure	Used for novel or not otherwise specified molecular assays when specific CPT codes are not applicable.
`89048`	Specimen handling (for molecular assays)	Ancillary code representing specialized specimen handling steps that may be billed with complex genomic tests.

OpenPayer

Summary & Overview

CPT 81349: Low‑Pass Whole Genome Sequencing for CNV and Homozygosity