Summary & Overview
CPT 0235U: PTEN Genomic Unity® Whole Genome Sequencing Analysis
CPT code 0235U denotes a Proprietary Laboratory Analyses (PLA) test — Genomic Unity® PTEN Analysis from Variantyx Inc. This PLA-level molecular diagnostic uses PCR-free whole genome sequencing of blood or saliva with algorithmic analysis to detect variants in the PTEN gene, which are clinically relevant for conditions such as hamartoma tumor syndrome. Nationally, PLA codes are important because they identify single-vendor tests with unique clinical claims and billing implications for payers, laboratories, and clinicians.
Key payers in this analysis include Aetna, Blue Cross Blue Shield plans, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the clinical intent and testing methodology, payer coverage context, and the typical service and site-of-service considerations for laboratory and genomic sequencing claims. The publication summarizes benchmark and policy implications relevant to PLA-coded genomic testing and clarifies the operational aspects of submitting the test from specimen collection through laboratory processing. The content is intended to inform billing professionals, laboratory administrators, and policy analysts about the coding and clinical context of CPT code 0235U and what to expect when this specific PTEN sequencing assay appears on the claim stream.
Billing Code Overview
CPT code 0235U is a Proprietary Laboratory Analyses (PLA) code for the Genomic Unity® PTEN Analysis produced by Variantyx Inc. The test evaluates the PTEN gene for variants associated with conditions such as hamartoma tumor syndrome using a PCR-free whole genome sequencing (WGS) platform with algorithmic data analysis of a blood or saliva specimen.
Service Type: Molecular diagnostic — genomic sequencing test
Typical Site of Service: Clinical laboratory or reference testing laboratory; specimens collected at outpatient clinics or collection centers
Clinical & Coding Specifications
Clinical Context
A typical patient is an adult or pediatric individual referred for targeted PTEN gene analysis because of personal or family findings suggestive of PTEN hamartoma tumor syndrome (PHTS), Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, or early-onset breast, thyroid, or other PTEN-associated neoplasia. Referral commonly originates from a genetics clinic, oncology practice, endocrinology, pediatric neurology, or primary care following clinical features such as multiple hamartomas, macrocephaly, mucocutaneous lesions, unexplained intellectual disability with autistic features, or a family history of PTEN pathogenic variants.
The clinical workflow: the ordering clinician documents medical necessity and counseling, obtains informed consent, and collects a blood or saliva specimen per Variantyx Inc. instructions. The sample is shipped to the performing laboratory where a PCR-free whole genome sequencing (WGS) platform and algorithmic analysis evaluate the PTEN gene for single nucleotide variants, small insertions/deletions, and structural variants relevant to PHTS. The laboratory performs bioinformatic interpretation, classifies variants per ACMG/AMP guidelines, and issues a report with clinical interpretation, variant classification, and recommendations for follow-up testing or familial testing where applicable. Results are routed back to the ordering provider for patient management and genetic counseling.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
00 | Default modifier (no specific modifier) | Use when no other modifier applies to the service. |
22 | Increased procedural services | Use when the laboratory documents unusually high complexity or time for analysis or reporting beyond typical expectations.
26 | Professional component | Use when billing only the professional component of the test (interpretation) separate from the technical component.
52 | Reduced services | Use when the service performed is reduced or partially rendered compared with the full test.
53 | Discontinued procedure | Use when testing is started but discontinued for patient-related or specimen-related reasons.
62 | Two surgeons | Use when two providers with different specialties share responsibility for case-level decisions; rarely applicable but available if two qualified physicians co-manage interpretation.
78 | Return to operating room for a related procedure | Not typically used for lab testing; included when clinically relevant to related surgical follow-up billing.
80 | Assistant surgeon | Rarely applicable to laboratory services; used when an assistant surgeon participates in a related operative procedure.
82 | Assistant surgeon (when qualified resident not available) | As above, related to operative claims that may be billed alongside genetic testing in the care episode.
AS | Physician assistant, nurse practitioner, or clinical nurse specialist services for assistant at surgery | Generally not applicable to this lab test; included for completeness when clinical episode includes surgical services.
QK | Medical direction of two, three, or four cytotechnologists | Not applicable to WGS PTEN testing; included only when specific laboratory staffing modifiers apply per payer rules.
QX | Certified nurse-midwife, clinical nurse specialist, nurse practitioner service with modifier for practitioner | May be used when such practitioners order or interpret the test under local payer rules for professional billing.
QY | Claim by a hospital when employer-based independent lab performs the test | Use when billing arrangements require a lab-performed test billed under hospital outpatient claims.
TC | Technical component | Use when billing only the technical component (laboratory processing/sequencing) separate from interpretation.
| Taxonomy Code | Specialty | Notes |
|---|---|---|
207L00000X | Clinical Geneticist | Ordering and interpreting germline PTEN testing; directs genetic counseling. |
2080P0207X | Pediatrician | Often initiates testing for developmental delay or macrocephaly in children.
207K00000X | Medical Oncologist | Orders PTEN testing for hereditary cancer risk assessment in patients with early-onset or multiple primary tumors.
207RG0300X | Endocrinologist | Manages thyroid disease or other endocrine manifestations prompting PTEN evaluation.
363L00000X | Laboratory Geneticist/Clinical Molecular Geneticist | Oversees laboratory test validation, interpretation, and reporting.
Related Diagnoses
| ICD-10 Code | Description | Clinical Relevance |
|---|---|---|
Q85.8 | Other phakomatoses, not elsewhere classified | May be used for syndromic hamartomatous conditions when PTEN-related hamartoma tumor syndromes are considered. |
D17.9 | Benign lipomatous neoplasm, unspecified | PTEN mutations can present with multiple benign neoplasms; used when benign tumor burden prompts genetic evaluation.
R62.0 | Delayed milestone in childhood | Developmental delay or autism spectrum features with macrocephaly can prompt PTEN testing in pediatric patients.
E66.9 | Obesity, unspecified | Macrocephaly and developmental concerns in some PTEN-related conditions may co-occur with obesity; used as comorbidity in the clinical picture.
C50.919 | Malignant neoplasm of unspecified site of female breast | Early-onset breast cancer or family history of breast cancer may trigger hereditary PTEN testing as part of cancer risk assessment.
C73 | Malignant neoplasm of thyroid gland | Thyroid cancers, particularly in younger patients or with personal/family history, are relevant to PTEN-associated syndromes.
Related CPT Codes
| CPT Code | Description | Relationship to This Procedure |
|---|---|---|
0235U | Genomic Unity® PTEN Analysis — PCR-free whole genome sequencing from Variantyx Inc. | The primary PLA code for this proprietary PTEN assay; billed for the laboratory's sequencing and analytic service when performed by the specified manufacturer/lab. |
81162 | BRCA1 and BRCA2 analysis, full sequence; single gene sequencing when ordered as reflex or separate hereditary cancer testing | May be ordered in the same hereditary cancer workup when PTEN testing is performed alongside broader hereditary panels or if family history indicates additional genes.
81403 | Exome or targeted sequence analysis, 5-50 genes (tiered panel) | Used when broader multigene panels are performed in parallel or as confirmatory/expanded testing beyond single-gene PTEN analysis.
81225 | APC (adenomatous polyposis coli) gene analysis | Ordered in differential hereditary gastrointestinal polyposis workups where clinical features overlap with PTEN-associated syndromes.
81161 | MSH6, MSH2, MLH1, PMS2 analysis (selected genes) | May be relevant when hereditary cancer syndromes are considered and additional mismatch repair gene testing is performed as part of comprehensive evaluation.
G0452 | Genetic counseling service(s), each 30 minutes (Add-on for Medicare where applicable) | Used to bill for face-to-face genetic counseling sessions that accompany ordering and result disclosure for hereditary PTEN testing.