Centene Carrier Screening Coverage Policy Update

Coverage Criteria

General Coverage Scope

Covered when consistent with policy definitions and appropriate indications (summary from available sections):

Coverage scope: Carrier screening (prenatal or preconception) to identify individuals at risk of having offspring with autosomal recessive or X-linked single-gene disorders; includes risk-based screening and expanded carrier screening panels; basic panels limited to not more than 14 genes for certain definitions.

Detailed clinical criteria and specific medical necessity rules are provided in individual sections for genes/panels (CFTR, SMN1, FMR1, HBA/HBB, DMD, Ashkenazi panel, expanded panels).

Expanded Carrier Screening - Medical Necessity

Expanded carrier screening panels (81243, 81257, 81329, 81443*) may be considered medically necessary when ALL of the following are met:

Expanded panel medical necessity: A. The member/enrollee is considering pregnancy or is currently pregnant; AND B. The panel includes the genes CFTR and SMN1.

Expanded carrier screening panels are considered investigational for all other indications. Fragile X (81243) and SMA (81329) may be billed with 81443 if performed separately per CPT guidelines.

General Criteria for Targeted Carrier Screening

Targeted carrier screening may be considered medically necessary when ALL of the following are met:

Targeted carrier screening general: A. The member/enrollee is considering pregnancy or is currently pregnant; AND B. The genetic disorder is a recessive condition with childhood onset; AND C. One of: (1) the member/enrollee has a close relative with a known pathogenic or likely pathogenic variant associated with the disorder; OR (2) the member/enrollee's reproductive partner is a carrier for the genetic disorder; OR (3) the member/enrollee or reproductive partner are members of a population with carrier rate ≥1%; OR (4) the member/enrollee or reproductive partner has a first- or second-degree relative affected with the genetic disorder.carrier frequency >= 1% for population criterion

If none of these criteria are met, targeted carrier screening is considered investigational.

Cystic Fibrosis (CFTR) Coverage

CFTR testing (targeted familial variant, sequencing, deletion/duplication, intron 9 polyT/TG) covered under specified conditions:

CFTR targeted familial variant (81221): Member and/or reproductive partner is considering pregnancy or is currently pregnant AND member has a close relative with a known pathogenic or likely pathogenic CFTR variant.

Targeted familial variant testing is investigational for other indications.

CFTR sequencing/deletion/duplication/mutation panel (81223, 81222, 81220): Member and/or reproductive partner is considering pregnancy or is currently pregnant OR the reproductive partner is a known carrier for cystic fibrosis; when using targeted approaches include at minimum the ACMG-23 variant panel.

Sequencing/deletion-duplication or mutation panel is investigational for other indications; reflex testing for 5T/7T/9T recommended when R117H positive per technical guidance.

CFTR intron 9 polyT/TG analysis (81224): Member and/or reproductive partner is considering pregnancy or is currently pregnant AND member is known to have the R117H variant in CFTR.

Intron 9 polyT/TG analysis is investigational for other indications.

Spinal Muscular Atrophy (SMN1/SMA) Coverage

SMN1 carrier screening (targeted and sequencing) covered under specified conditions:

SMN1 targeted variant analysis (81337, 81403): Member and/or reproductive partner is considering pregnancy or is currently pregnant AND member has a close relative with a known pathogenic or likely pathogenic SMN1 variant.

Targeted SMN1 testing is investigational for other indications.

SMN1 sequencing and/or deletion/duplication and SMN2 analysis (81329, 81336, 81401, 81405): Member and/or reproductive partner is considering pregnancy or is currently pregnant OR the reproductive partner is a known carrier for spinal muscular atrophy.

Sequencing/deletion-duplication analyses are investigational for other indications; SMA screening is recommended by ACOG for all individuals considering pregnancy or currently pregnant.

Fragile X (FMR1) Coverage

FMR1 CGG repeat analysis (81243, 81244) may be medically necessary when ANY of the following applies:

Fragile X indications: 1) Member diagnosed with premature ovarian insufficiency or elevated FSH before age 40; OR 2) Member is considering pregnancy or is currently pregnant AND has one of: a) close relative with Fragile X syndrome (>200 CGG repeats); b) close relative who is a known carrier (55-200 CGG repeats); c) close relative with unexplained intellectual disability, developmental delay, or autism; OR d) close relative diagnosed with premature ovarian insufficiency or elevated FSH before age 40.

Fragile X testing is investigational for other indications; follow-up genetic counseling recommended for intermediate/premutation/full mutation results.

Hemoglobinopathy Coverage

HBA1/HBA2 and HBB targeted and sequencing analyses covered when:

HBA/HBB targeted variant analysis (81257, 81258, 81361, 81362): Member and/or reproductive partner is considering pregnancy or is currently pregnant AND member meets one of: (1) close relative with known pathogenic/likely pathogenic HBA/HBB variant; OR (2) reproductive partner is a known carrier; OR (3) reproductive partner has a diagnosis of a hemoglobinopathy; OR (4) member's hematologic screening results (MCV, MCH, CBC, hemoglobin electrophoresis, or DCIP) are suggestive of or do not conclusively rule out a hemoglobinopathy.

Targeted HBA/HBB testing is investigational for other indications; perform hemoglobin electrophoresis when ethnicity or indices suggest hemoglobinopathy.

HBA/HBB sequencing/deletion-duplication analysis (81259, 81269, 81363, 81364): Member and/or reproductive partner is considering pregnancy or is currently pregnant AND member's hematologic screening results are suggestive of or do not conclusively rule out a hemoglobinopathy.

Sequencing/deletion-duplication analysis is investigational for other indications.

Ashkenazi Jewish Carrier Panel Coverage

Ashkenazi Jewish carrier panel (81412) may be considered medically necessary when ALL of the following are met:

Ashkenazi panel: Member and/or reproductive partner is considering pregnancy or is currently pregnant; AND member is of Ashkenazi Jewish ancestry; AND the panel includes, at minimum, ACMG-recommended screening for HEXA, ASPA, CFTR, ELP1, BLM, FANCC, SMPD1, GBA, and MCOLN1.

If only one partner is of Ashkenazi Jewish ancestry, testing that partner first is medically necessary; the other partner is tested only if the first partner is positive.

Duchenne/Becker Muscular Dystrophy (DMD) Coverage

Duchenne and Becker muscular dystrophy carrier screening covered under specified conditions:

DMD targeted variant analysis (81408, 81403): Member is considering pregnancy or is currently pregnant AND member has a close relative with a known pathogenic or likely pathogenic DMD variant.

Targeted DMD testing is investigational for other indications; when familial variant is known, test specific for that variant.

DMD sequencing and/or deletion/duplication analysis (81161, 81408, 0218U): Member is considering pregnancy or is currently pregnant AND member has a first- or second-degree male relative diagnosed with Duchenne or Becker muscular dystrophy.

When familial variant is unknown and an affected male is not available, perform CNV (deletion/duplication) analysis followed by sequencing (level 1 and 2) to achieve ~99% sensitivity per EMQN guidance.

Guideline-based coverage criteria

Covered when matching guideline recommendations are met

ACOG baseline recommendations: Offer carrier screening for cystic fibrosis and spinal muscular atrophy to all individuals considering pregnancy or currently pregnant; perform CBC and assess for hemoglobinopathy; offer fragile X premutation screening when family history or clinical indicators (e.g., ovarian insufficiency) present.

Sources: ACOG practice bulletins Nos. 690 and 691.

ACMG tiered screening: Offer Tier 3 carrier screening to all pregnant patients and those planning pregnancy; consider Tier 4 in consanguinity or when family/personal history warrants.

Source: ACMG practice resource (2021).

Condition-specific coverage and testing approach

Covered when testing aligns with recommended approaches and indications

CFTR testing: Offer CF carrier screening to women considering pregnancy or currently pregnant; when familial mutation known use targeted testing; for targeted approaches include at minimum the ACMG-23 variant panel; reflex 5T/7T/9T when R117H positive.

Sources: ACOG, ACMG technical standard, NSGC.

SMA (SMN1) testing: Offer SMA carrier screening to individuals considering pregnancy or currently pregnant; review molecular reports when family history exists and test at-risk partners accordingly; offer SMN1 deletion testing when familial reports unavailable.

Sources: ACOG, ACMG.

Fragile X (FMR1): Offer fragile X premutation screening to women with relevant family history or premature ovarian insufficiency; provide follow-up genetic counseling for intermediate, premutation, or full mutation carriers; offer prenatal diagnostic testing to known carriers.

Source: ACOG and NSGC guidance.

Carrier screening coverage criteria

Covered when testing follows professional guideline recommendations and is appropriate for the clinical context

DMD targeted testing when familial variant known: When the familial pathogenic DMD variant is known, carrier testing should be undertaken using a test specific for that variant.

Per EMQN and GeneReviews guidance.

DMD testing when familial variant unknown: When the familial pathogenic variant is unknown and an affected male is not available for testing, perform both CNV (deletion/duplication) analysis and sequencing (level 1 and 2 testing) to achieve approximately 99% sensitivity.~99% sensitivity when combined

EMQN guidance (2020).

Panel inclusion criteria: Conditions included on carrier screening panels should meet criteria such as carrier frequency ≥1/100, well-defined phenotype, detrimental effect on quality of life, cause cognitive or physical impairment, require intervention, or have early onset; panels should avoid primarily adult-onset conditions.

No explicit exclusions are listed in the excerpted coverage criteria. However, the policy notes that expanded carrier screening (ECS) panels vary in content and may include conditions that lack professional guideline support; that variability can affect whether specific panel items are considered appropriate for coverage decisions (ECS panels may include conditions that are not well understood and for which there are no existing professional guidelines).

The policy explicitly treats many tests as investigational (not covered) when their medical necessity criteria are not met. For example, expanded carrier panels are investigational for indications other than when the member is considering pregnancy or is pregnant and the panel includes CFTR and SMN1, and individual gene tests (CFTR, SMN1, FMR1, HBA/HBB, DMD) are investigational when the specific targeted criteria listed in each section are not satisfied (e.g., not pregnant/not considering pregnancy, no relevant family history, partner not a known carrier).

The American College of Medical Genetics and Genomics (ACMG) guidance cited in the policy recommends a tiered approach to carrier screening and does not support offering lower-tier (Tier 1 or 2) screening without Tier 3. ACMG also advises against routine offering of Tier 4 panels except in specific circumstances such as consanguinity or pertinent family/personal history, meaning routine pan-ethnic offering of very large panels is not recommended.

Professional guidance (ACOG practice bulletin) states that carrier screening panels should not include conditions primarily associated with adult-onset disease. Panel selection should favor disorders with early onset, well-defined phenotype, and significant impact on quality of life, consistent with the policy's panel inclusion criteria.

Within the excerpt window there is no discrete list labeled as 'not medically necessary.' The document instead focuses on conditions for which testing is considered medically necessary and highlights that tests and panel components falling outside those criteria are considered investigational.

The policy indicates that expanded carrier panels and targeted tests are considered investigational (not medically necessary) when the specific medical necessity criteria for each gene or panel are not met. Each gene-specific section (for CFTR, SMN1, FMR1, HBA/HBB, DMD, etc.) defines the circumstances under which targeted testing is medically necessary; absence of those indications renders testing investigational.

ACMG guidance referenced in the policy states that routine offering of Tier 4 expanded panels is not recommended; Tier 4 should generally be reserved for specific situations such as consanguinity or when family/personal history justifies broader screening.

The National Society of Genetic Counselors (NSGC) position, as cited in the policy, recommends that predictive genetic testing of minors for adult-onset conditions be deferred unless results will impact childhood medical management or provide significant benefit to the child; testing should generally wait until the individual can meaningfully consent.

Coding and Billing

Expanded Carrier Screening - Example/Common CPT CodesCPT

81243	No description provided in window (listed as common CPT for expanded carrier panels)
81257	No description provided in window (listed as common CPT for expanded carrier panels)
81329	No description provided in window (listed as common CPT for expanded carrier panels)
81443	No description provided in window (listed as common CPT for expanded carrier panels)

Basic Carrier Screening - Example/Common CPT CodesCPT

81220	Referenced for basic carrier screening panels
81329	Referenced for basic carrier screening panels
81243	Referenced for basic carrier screening panels
81257	Referenced for basic carrier screening panels

Common ICD CodesICD-10

O09	Pregnancy-related ICD code referenced for carrier screening
Z13	Encounter for screening for genetic and chromosomal anomalies (ICD) referenced
Z31	Encounter for procreation testing and counseling (ICD) referenced
Z34	Encounter for supervision of normal pregnancy (ICD) referenced
Z36	Antenatal screening of mother (ICD) referenced
Z84	Family history of genetic disease (ICD) referenced

Additional CPT/HCPCS codes referenced for specific gene testsmixed

81259	Referenced for HBA1/HBA2/HBB sequencing and/or deletion/duplication analysis
81269	Referenced for HBA1/HBA2/HBB sequencing and/or deletion/duplication analysis
81363	Referenced for HBA1/HBA2/HBB sequencing and/or deletion/duplication analysis
81364	Referenced for HBA1/HBA2/HBB sequencing and/or deletion/duplication analysis
81412	Referenced for Ashkenazi Jewish carrier panel testing
81408	Referenced for DMD targeted variant/sequencing
81161	Referenced for DMD sequencing and/or deletion/duplication analysis
0218U	Referenced for Genomic Unity DMD Gene Analysis (Variantyx)

Expanded carrier panel CPTsCPTCovered

81243	FMR1 (Fragile X) CGG repeat analysis / carrier screening
81257	HBA1/HBA2 targeted variant analysis (hemoglobinopathy)
81329	SMN1 sequencing and/or deletion/duplication analysis (SMA)
81443	Expanded carrier screening panel (panel CPT placeholder)

Covered and referenced CPTs for targeted/basic testingCPTCovered

81220	Mutation panel (CFTR) / basic panel
81221	CFTR targeted mutation analysis (known familial variant)
81222	CFTR deletion/duplication analysis
81223	CFTR sequencing
81224	CFTR intron 9 polyT and TG analysis
81337	SMN1 targeted variant analysis
81403	SMN1 targeted analysis (alternate code listed in policy)
81336	SMN2 deletion/duplication analysis
81401	SMN1 sequencing/deletion duplication (panel code listed)
81405	SMN2 analysis (additional code listed)

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Basic panel gene count threshold

Basic panel gene-count thresholdBasic carrier screening panels are limited to not more than 14 genes (covers CFTR, SMN1/2, FMR1, HBA/HBA2/HBB and related tests)

Typical included genes/targetsCFTR, SMN1/2, FMR1, HBA1/HBA2, HBB (examples listed in policy)

Representative CPTs for basic panelsCommon CPTs associated with basic panels: 81220, 81329, 81243, 81257

Example commercial basic panelsInheritest Core Panel (LabCorp), Inheritest Carrier Screen (14-gene society-guided, LabCorp), Prenatal Carrier Panel (Quest), Foresight Fundamental Panel (Myriad), Core Carrier Screen (Invitae)

Basic panel gene limit

Basic panel gene limitBasic carrier screening panels defined as CFTR, SMN1/2, FMR1, HBA/HBA2/HBB but not more than 14 genes

Policy handling of basic panelsBasic panels should be evaluated by the individual test criteria in the policy rather than treated as a single omnibus panel

Associated CPT codes81220, 81329, 81243, 81257 are cited as common CPT codes for these basic panels

Clinical scopeIntended for prenatal or preconception carrier screening covering cystic fibrosis, SMA, fragile X, and hemoglobinopathies within the gene-count limit

Provider Actions and Documentation

Prior Authorization

Prior authorization note for DMD full testing

Prior authorization may be required for Duchenne muscular dystrophy (DMD) full testing. When ordering full DMD testing in the absence of a known familial pathogenic variant, document the clinical rationale for performing both deletion/duplication (CNV) analysis and sequencing. Per EMQN guidance, when the familial pathogenic variant is unknown and an affected male is not available, offer the full cohort of level 1 and 2 genetic testing (CNV analysis plus sequencing) because together they achieve ~99% sensitivity.

Affected codes: 81161, 81408, 0218U
Document why targeted testing is not appropriate (e.g., familial variant unknown, affected relative unavailable)

Prior Authorization

Prior authorization: DMD targeted vs full testing

Prior authorization should distinguish targeted DMD testing (for a known familial pathogenic variant) from full DMD testing. If a familial pathogenic variant is known, targeted testing for that specific variant is the appropriate first step and should be requested. Full CNV plus sequencing testing should be reserved for cases where the familial variant is unknown or when directed testing would not detect the expected alteration.

Targeted codes (when familial variant known): 81408, 81403
Full testing codes (when familial variant unknown or affected male unavailable): 81161, 81408, 0218U

Denial Risk

Coding guidance and potential denial risk

Inclusion or exclusion of codes in this policy does not guarantee coverage. Providers should reference current coding guidance prior to claim submission. Failure to follow coding guidance or payer-specific prior authorization requirements may result in claim denial.

Codes listed are informational only; verify applicability and bundling rules prior to billing
Commonly referenced DMD codes: 81161, 81408, 0218U

Denial Risk

Failure to document family history, ancestry, or counseling may lead to denial

Failure to document family history, ancestry, counseling, or that screening was offered and discussed may lead to denial of coverage. Maintain documentation of the family history review, ancestry, counseling notes, and reasons for the selected testing strategy in the medical record.

Document whether genetic counseling was offered or provided
Document ancestry and detailed family history (degree of relation and affected/known carrier status)

Documentation Required

Document indication and test details

Document the clinical indication and test details when ordering carrier screening. Include appropriate ICD-10 diagnosis codes (e.g., O09, Z13, Z31, Z34, Z36, Z84), the specific test or panel ordered, and the clinical context (preconception vs prenatal).

List test name and genes included (e.g., CFTR, SMN1 included for expanded panels)
Include pregnancy or preconception status and rationale for panel selection

Documentation Required

Document family/partner carrier status

Document family and partner carrier status. When a close relative or reproductive partner is known to carry a pathogenic or likely pathogenic variant (e.g., CFTR, SMN1, DMD), record the relative's relationship, the specific variant if known, and any prior genetic test reports. This information guides whether targeted testing is appropriate.

Include degree of relation (first-, second-, third-degree) and whether the variant is confirmed pathogenic/likely pathogenic
Attach or summarize prior genetic test reports when available

Documentation Required

Document family history review and whether familial pathogenic variant is known

Document family history review and whether a familial pathogenic variant is known. If a familial variant is known, note that targeted testing was performed. If unknown, document offering of full CNV plus sequencing testing and the patient's/partner's decision.

If familial variant known → indicate targeted test ordered and code
If familial variant unknown → indicate full testing rationale and codes (CNV + sequencing)

Step Therapy

Stepwise DMD testing

For dystrophinopathies (DMD/BMD), follow stepwise testing: perform deletion/duplication (CNV) analysis first because most pathogenic variants are exon-level deletions, and proceed to sequencing if CNV analysis is negative. Document this stepwise approach in the record and the rationale for proceeding to sequencing when indicated.

Step 1: Deletion/duplication (CNV) analysis — commonly billed as 81408/81161
Step 2: Sequence analysis if no pathogenic CNV identified — commonly billed as 0218U/81161 depending on platform

OpenPayer

CONCERT GENETIC TESTING: PRENATAL AND PRECONCEPTION CARRIER SCREENING

Coverage Criteria

Covered Indications

Coding and Billing

Provider Actions and Documentation