CurrentCapital BluecrossPolicy MP 2.255

Genetic testing for PTEN hamartoma tumor syndrome

Defines medical necessity and coding for PTEN genetic testing to confirm PHTS (including Cowden syndrome, BRRS, Proteus/Proteus-like) and testing of first-degree relatives for a known familial PTEN pathogenic variant. Applies to products administered by Capital BlueCross (with product-specific variations noted).

Policy Summary

PayerCapital Bluecross

PolicyGenetic testing for PTEN hamartoma tumor syndrome

Policy CodePolicy MP 2.255

Change TypeNo material clinical changes

Effective DateJul 1, 2025

Next Review Date

Key ActionDocument clinical features consistent with PHTS or the known familial PTEN pathogenic/likely pathogenic variant and verify member benefits prior to ordering testing.

SourceLink

1Policy number (MP 2.255)

2025-07-01Effective date

3Primary covered indications (proband confirmation, familial targeted testing, testing strategy steps)

>=10%Promoter variants detection rate in Cowden patients without identifiable coding-region variant

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Medically necessary - Proband diagnostic testing

Genetic testing for a PTEN mutation is considered medically necessary to confirm the diagnosis when ALL of the following are met:

ALL of the following

Individual has clinical signs of a PTEN hamartoma tumor syndrome (PHTS) including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), or Proteus-like syndrome (PLS).
Clinical diagnosis is phenotypic; definitive diagnosis requires identification of a PTEN disease-associated variant.

Medically necessary - Targeted familial testing

Targeted genetic testing for a known familial PTEN variant is considered medically necessary when ALL of the following are met:

ALL of the following

Individual is a first-degree relative of a proband with a known PTEN pathogenic or likely pathogenic familial variant.

Investigational / Not covered indications

Genetic testing for PTEN is considered investigational / not covered for ALL other indications (i.e., indications not listed above):

ALL of the following

Any indication other than (1) confirmation of PHTS in a proband with clinical signs, or (2) targeted testing of an asymptomatic first-degree relative for a known familial PTEN pathogenic or likely pathogenic variant.

Testing strategy in a proband (sequencing order)

Recommended order of testing to optimize diagnostic yield in a proband:

ALL of the following

Step 1: Sequence PTEN exons 1–9 and flanking intronic regions.
If no disease-associated variant is identified → Step 2: Perform deletion/duplication analysis (PTEN deletion/duplication testing).
If no disease-associated variant is identified → Step 3: Consider promoter analysis.
Promoter variants account for approximately 10% of individuals with Cowden syndrome who do not have an identifiable coding-region PTEN disease-associated variant.

Procedure and Diagnosis Codes

Covered procedure/CPT/PLA codesmixedCovered

0235U	PLA code listed in policy (new PTEN-related PLA code)
81321	PTEN (PTEN) sequencing (procedure code mapping listed in policy)
81322	PTEN deletion/duplication analysis (procedure code mapping listed in policy)
81323	PTEN promoter analysis or other PTEN-related procedure (procedure code mapping listed in policy)

Relevant ICD-10 codes (supporting diagnoses/encounters)ICD-10

Q85.81	PTEN hamartoma tumor syndrome
Q85.82	Other Cowden syndrome
Q85.89	Other phakomatoses, not elsewhere classified
Q85.9	Phakomatosis, unspecified
Z13.71	Encounter for nonprocreative screening for genetic disease carrier status
Z13.79	Encounter for other screening for genetic and chromosomal anomalies

Documentation, Prior Authorization, and Counseling Requirements

Documentation Required

Document clinical signs for proband testing

Document and record the proband's clinical features consistent with PTEN hamartoma tumor syndrome (PHTS) using established diagnostic criteria (e.g., International Cowden Consortium criteria) — including major, minor, and pathognomonic findings (for example: macrocephaly, mucocutaneous lesions, Lhermitte‑Duclos disease, breast/thyroid/endometrial cancers, and specified counts of mucocutaneous lesions as listed in the Cowden criteria).

Use the International Cowden Consortium/Cowden syndrome criteria (pathognomonic, major, minor) to document signs.
Macrocephaly defined as occipital frontal circumference ≥97th percentile is a major criterion.
Pathognomonic mucocutaneous findings include trichilemmomas and ≥6 facial papules (with ≥3 trichilemmomas) or palmoplantar keratoses ≥6.

Documentation Required

Confirm familial variant for targeted testing

For targeted testing of an asymptomatic first‑degree relative, document the specific PTEN familial variant (pathogenic or likely pathogenic) that was identified in the proband to support medical necessity for targeted analysis.

Record the familial PTEN disease‑associated variant using HGVS nomenclature as reported in the proband.
Variant should be classified as pathogenic or likely pathogenic per ACMG‑AMP terminology for use in targeted testing.

Prior Authorization

Benefit/coverage verification required

Verify that the member's health benefit plan covers the requested PTEN testing and contact Capital BlueCross for benefit applicability before ordering; the existence of this medical policy does not guarantee coverage under a member's plan.

Benefit determinations are based on the applicable health benefit plan language and not the medical policy alone.
If unclear, contact Capital Blue Cross Provider Services or Member Services for plan‑specific coverage information prior to testing.

Documentation Required

Genetic counseling recommended

Provide or refer the patient for formal genetic counseling by a genetics professional prior to testing to ensure understanding of test implications and potential impact on family members.

Counseling should be performed by an individual experienced in genetic medicine and genetic testing methods.
Genetic counseling may alter utilization and reduce inappropriate testing and helps patients understand results and familial implications.

Clinical Background for PTEN and PHTS

PTEN hamartoma tumor syndrome (PHTS) is an inherited disorder caused by germline PTEN disease-associated variants and includes a spectrum of clinically overlapping syndromes such as Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and Proteus-like syndrome (PLS). PTEN is a tumor suppressor gene on chromosome 10q23 and variants are inherited in an autosomal dominant manner; PTEN is the only gene in which disease-associated variants are known to cause PHTS.

PHTS confers markedly increased lifetime cancer risks, most notably for breast, thyroid, and endometrial cancers. Published series report very high cumulative risks—for example, studies have estimated lifetime breast cancer risk around the mid-80% range and thyroid cancer risk in the 30–35% range for individuals with PTEN disease-associated variants. Because CS is associated with a documented cancer predisposition, patients with other PHTS diagnoses and PTEN variants are often assumed to have similar cancer risks.

The diagnosis of PHTS is suspected on clinical grounds using established phenotypic criteria (including pathognomonic mucocutaneous findings, major criteria such as macrocephaly—defined as occipital frontal circumference ≥97th percentile—and combinations of major/minor features), but a definitive diagnosis is made only by identification of a PTEN disease-associated variant.

Most PTEN disease-associated variants are identified by sequence analysis of the coding exons and flanking intronic regions; additional variants may be detected by deletion/duplication testing or promoter analysis. Reported test sensitivity varies by syndrome: detection rates are up to approximately 85% for Cowden syndrome and about 65% for BRRS, with lower and more variable detection in PS/PLS. Promoter variants account for about 10% of individuals with Cowden syndrome who lack an identifiable coding-region variant.

Identification of a PTEN disease-associated variant in a proband enables targeted testing of at-risk first-degree relatives to determine who should undergo initial evaluation and enhanced surveillance. Because PHTS manifestations are typically present by early adulthood—more than 90% of individuals with CS have clinical features by the late 20s—the primary clinical benefit of testing is to guide cancer surveillance and management.

Policy Summary

PayerCapital Bluecross

PolicyGenetic testing for PTEN hamartoma tumor syndrome

Policy CodePolicy MP 2.255

Change TypeNo material clinical changes

Effective DateJul 1, 2025

Next Review Date

Key ActionDocument clinical features consistent with PHTS or the known familial PTEN pathogenic/likely pathogenic variant and verify member benefits prior to ordering testing.

SourceLink

On This Page

OpenPayer

Genetic testing for PTEN hamartoma tumor syndrome

Medical Necessity Criteria for PTEN Testing

Procedure and Diagnosis Codes

Documentation, Prior Authorization, and Counseling Requirements

Clinical Background for PTEN and PHTS

Key Definitions

Policy Dates & History