ModifiedCentenePolicy N/A

Expanded Carrier Screening — Prenatal and Preconception

Coverage criteria and coding guidance for prenatal and preconception carrier screening (including expanded carrier screening) affecting individuals/couples seeking carrier testing prior to or during pregnancy.

Policy Summary

PayerCentene

PolicyExpanded Carrier Screening — Prenatal and Preconception

Policy CodePolicy N/A

Change TypeContent and coding updates (material and clarifying)

Effective Date

Next Review Date

Key ActionVerify clinical criteria and coding prior to submission; ensure panels meet specified gene requirements (e.g., CFTR + SMN1 for expanded panels) and document pregnancy/planning status.

SourceLink

POLICY UPDATE CHANGES

In the criteria for CFTR Sequencing, Deletion/Duplication Analysis, or Mutation Panel, changed the number of tested variants from 23 to 100 to align with 2023 ACMG guidance.

Updated HBA1/HBA2/HBB sequencing criteria to align with current ACOG recommendations for universal hemoglobinopathy screening.

Moved General Criteria for Targeted Carrier Screening to a separate policy ('Genetic Testing: General Approach to Genetic and Molecular Testing').

Added clarifying language that if CPT 81243 is billed with 81443, the patient should still meet Fragile X criteria.

Updated title to reflect V1.2025/V2.2024 versions and performed semi-annual review with multiple criteria and table updates.

Added CPT code 81361 to policy reference table and criteria set for basic carrier screening panels (to reflect inclusion of hemoglobinopathy tests on panel).

Clarified that if CPT 81243 is billed with 81443, the patient should still meet Fragile X criteria.

Added investigational criterion to Ashkenazi Jewish Carrier Panel Testing which was previously missing.

Clarified investigational statement for HBA1/HBA2/HBB testing does not include fetal hemoglobin testing via circulating fetal DNA.

Renamed CFTR Known Familial Variant Analysis to CFTR Targeted Variant Analysis and updated related headings and references.

Updated FMR1 Repeat Analysis criteria name to distinguish carrier screening from diagnostic testing and added a billing clarification.

1,300+inherited recessive disorders referenced

100minimum CFTR variants recommended

≤14Basic panel max genes

81361CPT added to basic panels

CFTR + SMN1Required genes for expanded panels

Semi-annualpolicy review frequency

Coverage Criteria — Expanded and Basic Carrier Screening

Expanded Carrier Screening - Medical Necessity

Expanded carrier screening panels may be considered medically necessary when:

Expanded panel criteria: Member is considering pregnancy or is currently pregnant AND panel includes CFTR and SMN1.

Panels listed: 81243,81257,81329,81336,81405,81408,81479,0400U,81443

Basic Carrier Screening - Medical Necessity

Basic carrier screening panels (CFTR, SMN1/2, FMR1, HBB/HBA1/HBA2, not more than 14 genes) may be considered medically necessary when:

Basic panel criteria: Member or reproductive partner is considering pregnancy or is currently pregnant.<=14 genes

Codes: 81220,81222,81223,81243,81257,81329,81336,81361,0449U

CFTR Targeted Variant Analysis

CFTR targeted variant analysis (81221) may be considered medically necessary when:

CFTR targeted: Member 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.

81221 considered investigational for other indications

CFTR Sequencing/Deletion/Duplication/Panel

CFTR sequencing, deletion/duplication, or mutation panel may be considered medically necessary when:

CFTR sequencing/dup/ panel criteria: (A) Member or reproductive partner is considering pregnancy or is currently pregnant OR (B) reproductive partner is a known carrier for cystic fibrosis.ACMG-100 variant panel minimum for mutation panel

Investigational for other indications

CFTR Intron 9 polyT/TG Analysis

CFTR intron 9 polyT and TG analysis (81224) may be considered medically necessary when:

CFTR intron 9: Member or reproductive partner is considering pregnancy or is currently pregnant AND member is known to have an R117H CFTR variant.

Investigational for other indications

SMN1 Targeted Variant Analysis

SMN1 targeted variant analysis may be considered medically necessary when:

SMN1 targeted: Member 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.

81337,81403; investigational for other indications

SMN1 Sequencing/Del-Dup and SMN2 Analysis

SMN1 sequencing and/or deletion/duplication and SMN2 analysis may be considered medically necessary when:

SMN1 sequencing/SMN2 analysis: (A) Member or reproductive partner is considering pregnancy or is currently pregnant OR (B) reproductive partner is a known carrier for SMA.

Investigational for other indications; refer to condition-specific diagnostic policy for symptomatic testing

FMR1 Repeat Analysis for Carrier Screening

Fragile X (FMR1) repeat analysis may be considered medically necessary when:

FMR1 carrier: (A) Member diagnosed with premature ovarian insufficiency or elevated FSH before age 40 OR (B) Member is considering pregnancy or is currently pregnant AND has one of: close relative with Fragile X (>200 repeats), close relative carrier (55-200 repeats), close relative with unexplained ID/DD/ASD, or close relative with premature ovarian insufficiency or elevated FSH before 40.

81243,81244; investigational for other indications; billing note: if 81243 billed with 81443, Fragile X criteria still must be met

Hemoglobinopathy Carrier Screening

Hemoglobinopathy testing (targeted or sequencing/del-dup) may be considered medically necessary when:

HBA/HBB targeted: Member or reproductive partner is considering pregnancy or is currently pregnant AND member has a close relative with a known pathogenic or likely pathogenic variant in HBA1, HBA2, or HBB (for targeted).

Targeted codes investigational for other indications; sequencing/del-dup codes are medically necessary when member or partner is considering pregnancy or currently pregnant; excludes fetal hemoglobin testing via circulating fetal DNA

Ashkenazi Jewish Carrier Panel

Ashkenazi Jewish carrier panel testing (81412) may be considered medically necessary when:

Ashkenazi panel: Member or reproductive partner is considering pregnancy or is currently pregnant AND member is of Ashkenazi Jewish ancestry AND panel includes minimum recommended genes (HEXA, ASPA, CFTR, ELP1, BLM, FANCC, SMPD1, GBA, MCOLN1, G6PC1, TMEM216, BCKDHB, PCDH15, CLRN1).

If only one partner is Ashkenazi, testing that partner is sufficient; other partner tested only if result is positive

DMD Carrier Screening

DMD testing may be considered medically necessary when:

DMD targeted variant analysis (81479) when member is considering pregnancy or is currently pregnant AND member has a close relative with a known pathogenic or likely pathogenic DMD variant.

Investigational for other indications

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

Investigational for other indications

Professional society–aligned coverage criteria

Covered/Recommended when following professional society guidance

ACMG Tier 3 Offer: Offer Tier 3 carrier screening for autosomal recessive and X-linked conditions to all pregnant patients and those planning pregnancy.Tier 3 (1/200 carrier frequency or higher)

Includes Tier 1 and Tier 2 genes

ACOG Universal Offers: Offer cystic fibrosis and spinal muscular atrophy carrier screening to all women considering pregnancy or currently pregnant; offer hemoglobinopathy testing (CBC/hemoglobinopathy screening) to all patients considering pregnancy or currently pregnant.universal

Applies regardless of ethnicity

Targeted testing when familial variant known: If a familial pathogenic or likely pathogenic variant is known, follow-up partner testing should target analysis of that same gene/variant; review affected family member molecular reports when available and provide genetic counseling.

HBA1/HBA2/HBB Sequencing and/or Deletion/Duplication Analysis

Policy criteria updated or realigned; see individual criteria sets for full AND/OR logic.

HBA1/HBA2/HBB Sequencing/Del-Dup: Criteria updated to align with current ACOG recommendations for universal hemoglobinopathy screening

Investigational statement clarified to exclude fetal hemoglobin testing via circulating fetal DNA

FMR1 and CFTR Criteria Sets

Policy contains distinct criteria sets for carrier versus diagnostic FMR1 testing and for CFTR targeted variant analysis.

FMR1 Repeat Analysis for Carrier Screening: Criteria renamed/clarified to distinguish carrier screening from diagnostic testing; billing note: if 81243 billed with 81443, Fragile X criteria must still be met

CFTR Targeted Variant Analysis: Name changed from 'CFTR Known Familial Variant Analysis' to 'CFTR Targeted Variant Analysis' with updated headings and references

Basic Carrier Screening Panels

Basic Carrier Screening Panels updated.

Basic Carrier Screening Panels: Includes cystic fibrosis, spinal muscular atrophy, fragile X, hemoglobinopathies, not more than 14 genes; CPT 81361 added to reflect inclusion of hemoglobinopathy tests on panel<=14 genes

Expanded carrier screening (ECS) panels use next-generation sequencing to screen many genes simultaneously (panels can include up to hundreds of genes) and are not standardized. Because ECS panels may include conditions that are not well understood and for which there are no existing professional guidelines, panel composition can vary substantially and may include disorders outside established guidance.

Each specific test or panel described in this policy is considered investigational (not medically necessary) when performed for indications other than those explicitly listed. For example, expanded and basic carrier panels, targeted variant analyses, sequencing and/or deletion/duplication testing, FMR1 repeat analysis, DMD testing, and hemoglobinopathy testing are investigational outside the preconception/prenatal context or when required family-history/partner-carrier criteria are not met.

The American College of Medical Genetics and Genomics (ACMG) guidance referenced in the policy defines screening tiers and advises that Tier 3 screening (genes with ~1/200 carrier frequency or higher) be offered to all pregnant or planning-pregnancy patients. ACMG also advises against offering Tier 1 or Tier 2 alone without Tier 3 and does not recommend routine offering of Tier 4 panels.

The investigational statement for HBA1/HBA2/HBB sequencing and/or deletion/duplication analysis explicitly excludes fetal hemoglobin testing via circulating fetal DNA from the scope of that investigational language; sequencing/del-dup testing is considered investigational for other non-listed indications, but the exclusion clarifies that cfDNA-based fetal hemoglobin assays are not being referenced by this investigational statement.

Expanded carrier screening panels are considered investigational when used outside the listed indications (that is, outside preconception or prenatal testing and when the panel does not meet the policy’s gene requirements such as inclusion of CFTR and SMN1). Providers should note that expanded panels billed for non‑pregnancy or non‑planning indications may be denied as investigational.

Basic carrier screening panels (which include CFTR, SMN1/2, FMR1, and hemoglobinopathy genes and are limited to not more than 14 genes) are considered investigational for indications outside pregnancy or planning pregnancy. This aligns with ACOG/ACMG guidance that universal offers (for CF and SMA) apply in the prenatal/preconception context and that routine extended tier 4 offerings are not recommended.

The policy removed or reclassified several previously listed broad/commercial panels and specific CPT references and marked some uses investigational or unsupported where criteria are not met. Sequencing and deletion/duplication testing that fall outside guideline-aligned indications were clarified as investigational in the updated reference tables and criteria.

An investigational criterion was added for some uses of the Ashkenazi Jewish carrier panel testing (81412). The policy clarifies that Ashkenazi panel testing is medically necessary only for members of Ashkenazi Jewish ancestry who are considering pregnancy or currently pregnant and when the panel includes the minimum recommended genes; other uses may be investigational.

Covered Indications and Offer Recommendations

inv-59: Preconception or prenatal carrier screening to identify individuals at risk of having offspring with inherited disorders

Preconception or prenatal carrier screening to identify individuals at risk of having offspring with inherited recessive or X-linked single-gene disorders.

Purpose: Screen asymptomatic individuals to identify carrier status for autosomal recessive or X-linked single-gene disorders to estimate reproductive risk.

Risk-based screening when increased carrier risk due to population frequency, ethnicity, or family history

Couple approach: If one partner is high-risk due to ancestry or family history, offer testing to that partner; if found to be a carrier, offer testing to the reproductive partner.

Genetic counseling strongly recommended

inv-60: Preconception or prenatal carrier screening — coverage when considering pregnancy or currently pregnant

Preconception or prenatal carrier screening — coverage when considering pregnancy or currently pregnant

Eligibility Requirements and Preconditions

Testing is offered when there is a family history of a condition; specifically, many targeted tests require that a close relative have a known pathogenic or likely pathogenic variant in the gene being tested. If one partner is high-risk due to ancestry or family history and is a confirmed carrier, the reproductive partner should be offered testing appropriate to that familial variant or panel.

No top-level eligibility requirement nodes are listed in this portion of the document beyond the specific test criteria and family-history/partner-carrier guidance described elsewhere in the policy.

Consistent with covered indications, testing is offered when the member or reproductive partner is considering pregnancy or is currently pregnant and when a close relative has a known pathogenic or likely pathogenic variant in the gene of interest; this supports targeted testing rather than broad panels when a familial mutation is known.

The policy does not state explicit prior testing prerequisites for most tests. When a familial pathogenic variant is known, targeted testing of that familial variant is expected rather than broad panel testing; if affected relative molecular reports are unavailable, providers are advised to review available reports and conduct targeted analysis of the same gene/variant.

No additional top-level eligibility nodes are present here; refer to the specific test criteria and the general genetic testing policy for general eligibility requirements.

Again, there are no explicit prior testing prerequisites across the policy; however, when a familial pathogenic variant is known, follow-up testing should target that variant and the laboratory method selected must include detection of the familial mutation.

Coding — CPT, PLA, and Diagnosis Codes

Example CPT/PLA codes referenced for carrier screeningmixed

81329	Example common CPT for Expanded Carrier Screening panels
81443	Example common CPT for Expanded Carrier Screening panels
81412	Ashkenazi Jewish Carrier Panel Testing (example CPT referenced)
81221	CFTR targeted variant analysis (example mapping)
81222	CFTR sequencing deletion/duplication (example mapping)
81223	CFTR complete rare variant analysis (example mapping)
81224	CFTR intron polyT/TG analysis (example mapping)
81243	FMR1 repeat analysis (example mapping)
81244	FMR1 repeat analysis variant (example mapping)
81257	HBA/HBB targeted variant analysis (example mapping)

1–10 of 21

1/3

Example ICD codes referencedICD-10

O09	Example ICD code for pregnancy-related carrier screening
Z13	Example ICD code for screening
Z31	Example ICD code for encounter for procreative management
Z34	Example ICD code for supervision of normal pregnancy
Z36	Encounter for antenatal screening of mother
Z84	Family history of genetic disease
Z83.49	Family history related code example (CFTR mapping)

Expanded Carrier Screening / related codesmixed

81243	Fragile X (FMR1) repeat analysis
81257	HBA1/HBA2 targeted analysis (hemoglobinopathy)
81329	SMN1 sequencing/deletion-duplication (SMA)
81336	SMN2 or related analysis
81405	Targeted gene panel, multiple genes
81408	DMD sequencing and/or del/dup
81479	DMD targeted variant analysis
0400U	PLA code listed with expanded panels
81443	Unlisted large panel code referenced

Basic Carrier and gene-specific testing codesmixed

81220	Carrier screening, mutation panel
81222	CFTR deletion/duplication analysis
81223	CFTR sequencing
81221	CFTR targeted variant analysis (known familial variant) [referenced in text]
81224	CFTR intron 9 polyT and TG analysis
81337	SMN1 targeted variant analysis
81403	SMN1 targeted variant analysis (alternate)
0236U	SMN-related PLA code
81244	FMR1 diagnostic/other repeat analysis
81257	HBA1 targeted variant analysis

1–10 of 20

1/2

Diagnosis/ICD codes referencedICD-10

O09	Pregnancy-related diagnosis code referenced
Z13	Encounter for screening for other diseases and disorders
Z31	Encounter for procreative management
Z34	Encounter for supervision of normal pregnancy
Z36	Encounter for antenatal screening of mother
Z84	Family history of genetic and other diseases

Referenced CPT/HCPCS codes (policy edits and references)mixed

81222	CFTR (examples added to basic panel list)
81223	CFTR (examples added to basic panel list)
81243	FMR1 analysis (Fragile X)
81329	historically used/removed from some lists
81336	added to Expanded Carrier Screening Panels
81405	added to Expanded Carrier Screening Panels
81408	added to Expanded Carrier Screening Panels (later removed/changed in places)
81479	added for DMD sequencing/deletion-duplication analyses
0236U	added to SMN1/SMN2 testing entries

Updated/Referenced CPT CodesCPT

81361	Hemoglobinopathy testing (added to Basic Carrier Screening Panels)
81243	FMR1 testing (Fragile X) — referenced in billing clarification
81443	CPT code that may be billed with 81243 — billing clarifications apply

Panel size (genes)

Typical content variationPanels can include conditions at population‑specific increased frequency as well as many conditions for which the individual is not at increased risk.

MethodNext‑generation sequencing is the common method used for ECS to analyze many genes simultaneously.

Clinical implicationNegative/normal results reduce but do not eliminate residual carrier risk; residual risk depends on test coverage and patient ethnicity.

Maximum genes in Basic panel

Provider Actions, Documentation & Billing Notes

Documentation Required

Coding examples require verification

Coding examples in this document are illustrative and require verification prior to claim submission. CPT codes and descriptions may change; providers should reference the current CPT manuals and the most up-to-date professional coding guidance before billing.

Codes listed are examples only and not comprehensive.
Inclusion of a code in the policy is not a guarantee of coverage.

Documentation Required

Carrier screening codes require clinical criteria

Carrier screening CPT codes included in the policy (for example 81220, 81221, 81222, 81223, 81243, 81257, 81329, 81336, 81361, 81405, 81408, 81443, 81479, 0400U, 0449U) must be supported by the clinical criteria described in this policy and any applicable general genetic testing criteria. Coding alone is not sufficient to determine coverage.

Background and Definitions

Carrier screening identifies asymptomatic individuals who carry pathogenic variants for autosomal recessive or X-linked single‑gene disorders to estimate reproductive risk. Expanded carrier screening (ECS) tests many genes simultaneously by next‑generation sequencing, panels vary in content, and negative results reduce but do not eliminate residual risk. Professional society guidance (ACMG/ACOG) underpins the policy’s testing recommendations.

Expanded carrier screening (ECS)

DefinitionExpanded carrier screening (ECS) involves screening individuals or couples for disorders in many genes simultaneously (up to 100s) using next‑generation sequencing; panels are not standardized.

ScopeECS panels may include conditions present with increased frequency in specific populations and many other conditions for which the individual may not be at increased risk.

Clinical noteProfessional societies recommend offering carrier screening prior to pregnancy; ECS content and nomenclature are evolving (policy aligns to ACMG/ACOG guidance).

Residual risk

Not Covered / Investigational Uses

Within the document window reviewed there are no explicit ‘not covered’ tests or indications listed as a standalone category; instead, many tests and panels are described as investigational when used outside the policy’s stated indications.

Tests and panels are considered investigational when used outside the listed indications—primarily when performed for patients who are not considering pregnancy or currently pregnant, or when required family‑history or partner‑carrier criteria are not met. Providers should expect investigational determinations for such use cases.

The ACMG guidance noted in the policy recommends against offering Tier 1 or Tier 2 screening without Tier 3 and does not support routine offering of Tier 4 panels. Practically, this means routine offering of very large or lower‑priority tier panels is not supported by professional guidance and may be considered inappropriate outside specified indications.

The investigational/not‑medically‑necessary language for HBA1/HBA2/HBB sequencing and/or deletion/duplication testing was clarified to state that it does not include fetal hemoglobin testing via circulating fetal DNA. That exclusion distinguishes molecular hemoglobinopathy sequencing from cfDNA fetal hemoglobin assays in the policy wording.

Policy Summary

PayerCentene

PolicyExpanded Carrier Screening — Prenatal and Preconception

Policy CodePolicy N/A

Change TypeContent and coding updates (material and clarifying)

Effective Date

Next Review Date

Key ActionVerify clinical criteria and coding prior to submission; ensure panels meet specified gene requirements (e.g., CFTR + SMN1 for expanded panels) and document pregnancy/planning status.

SourceLink

On This Page

familial variant known

Use targeted methods if familial variants are confirmed in both biological parents or affected sibling

Fragile X indications: Offer Fragile X (FMR1 repeat) carrier screening to women with family history of fragile X-related disorders or intellectual disability suggestive of fragile X, women with unexplained ovarian insufficiency or elevated FSH before age 40, and provide genetic counseling for intermediate/premutation/full mutation results.clinical/family history indications

Prenatal diagnostic testing offered to known carriers

SMN1/SMA screening: Offer SMA screening to all women considering pregnancy or currently pregnant; if family history of SMA, review molecular testing and recommend SMN1 deletion testing for low-risk partner if reports unavailable.universal/positive family history

ACOG/ACMG support

Coverage condition: Expanded and basic panels are covered when the member or reproductive partner is considering pregnancy or currently pregnant; expanded panels must include CFTR and SMN1.

Expanded panels investigational for other indications

inv-61: Ancestry-based (Ashkenazi) carrier screening

Ancestry-based (Ashkenazi) carrier screening

Ashkenazi ancestry: Member of Ashkenazi Jewish ancestry; panel must include specified genes (see list) as recommended by ACOG.

If only one partner is Ashkenazi, testing that partner is sufficient; other partner tested only if result is positive

inv-62: Targeted family-history directed testing

Targeted family-history directed testing

Close-relative directed testing: Covered when a close relative has a known pathogenic or likely pathogenic variant in the gene tested; documentation should identify degree of relationship.

Review affected relative molecular reports when available; use targeted methods for known familial variants

inv-63: Universal offer for CF and SMA and Tier 3 carrier screening per professional guidance

Universal offer for CF and SMA and Tier 3 carrier screening per professional guidance

ACMG Tier 3: Offer Tier 3 carrier screening for autosomal recessive and X-linked conditions to all pregnant patients and those planning pregnancy.Tier 3 (1/200 carrier frequency or higher)

Includes Tier 1 and Tier 2 genes

ACOG universal offers: Offer cystic fibrosis and spinal muscular atrophy carrier screening to all women considering pregnancy or currently pregnant; offer hemoglobinopathy testing at initial prenatal visit.universal

Applies regardless of ethnicity

inv-64: Fragile X (FMR1) carrier testing covered indications

Fragile X (FMR1) carrier testing covered indications

Fragile X indications: Women with family history suggestive of fragile X, unexplained early ovarian insufficiency, or elevated FSH before age 40; provide genetic counseling and offer prenatal diagnostic testing to known carriers.

Follow ACOG/ACMG guidance; billing clarification applies when 81243 billed with panel codes

inv-65: Hemoglobinopathy screening at initial prenatal visit or preconception (universal testing)

Hemoglobinopathy screening at initial prenatal visit or preconception (universal testing)

Universal hemoglobinopathy testing: Offer hemoglobinopathy testing (CBC/hemoglobinopathy screening) to all patients considering pregnancy or currently pregnant; molecular testing (sequencing/del-dup) medically necessary when member or partner is considering pregnancy.

Excludes fetal hemoglobin testing via circulating fetal DNA

inv-66: Basic carrier screening including CF, SMA, Fragile X, hemoglobinopathies (panels up to 14 genes)

Basic carrier screening including CF, SMA, Fragile X, hemoglobinopathies (panels up to 14 genes)

Basic panel inclusion: Basic carrier screening includes CFTR, SMN1/2, FMR1, and HBB/HBA1/HBA2 and is limited to panels not more than 14 genes; CPT 81361 added to reflect hemoglobinopathy inclusion.<=14 genes

Panels investigational for other indications

Basic carrier screening panels are limited to not more than 14 genes (e.g., CFTR, SMN1/2, FMR1, HBB/HBA1/HBA2), and are described as ≤14 genes in the policy.

Example codesBasic panel examples listed: 81220, 81222, 81223, 81243, 81257, 81329, 81336, 81361, 0449U.

Panel purposeDesigned to cover core conditions (cystic fibrosis, SMA, Fragile X, hemoglobinopathies) for preconception/prenatal screening.

Minimum CFTR variant set

Minimum CFTR variant setACMG recommends a minimum CFTR variant set of 100 variants when carrier testing is pursued (the 2023 ACMG position statement supersedes the prior 23‑variant set).

Reference standardThis 100‑variant minimum is specified in the ACMG 2023 CFTR variant testing position statement and technical guidance.

Implication for labsLaboratories performing CFTR carrier testing should include at least the ACMG‑recommended 100 variants for panels intended for carrier screening.

Basic Carrier Panel gene count

Basic Carrier Panel gene countBasic carrier screening panels include core genes for CF, SMA, Fragile X, and hemoglobinopathies and are limited to not more than 14 genes.

Included gene examplesPolicy examples for basic panels list CFTR, SMN1/2, FMR1, HBA1/HBA2/HBB among the genes covered.

CPT updateCPT code 81361 (hemoglobinopathy testing) was added to reflect inclusion of hemoglobinopathy tests on basic panels.

Ensure clinical documentation demonstrates the member is pregnant or considering pregnancy when required by criteria.
When billing targeted or familial variant testing, document the known familial pathogenic/likely pathogenic variant and relationship to the member.
Carrier screening performed for indications outside pregnancy/planning may be investigational per policy and require additional justification.

Prior Authorization

Prior authorization impact for panel CPT codes

Prior authorization requirements may be impacted by addition of panel CPT codes. When new panel codes (for example CPT 81361 added to basic panels) are billed, prior authorization routing and applicable criteria must be followed.

Obtain prior authorization according to the payer’s genetic testing or laboratory services prior authorization process when required.
If panels are split into component tests (e.g., billing 81243 or 81329 separately with 81443), ensure PA covers the combination and that specific disorder criteria (such as Fragile X) are met.
Updated coding may change PA form or required supporting documentation — verify with the payer before ordering.

Documentation Required

Coding inclusion is not a guarantee of coverage

Inclusion of a CPT code or test in the policy’s reference table is informational and does not guarantee coverage. Coverage determinations require that the submitted service and documentation meet the policy’s clinical criteria and any applicable general genetic testing policy requirements.

Reference table entries and example laboratory tests are provided to assist billing and claims navigation only.
Providers must supply clinical records, counseling notes, and family history as required by the policy during prior authorization and claims review.

Billing Rule

Coding/criteria alignment required

Coding and clinical-criteria alignment is required. Billing combinations and use of multiple CPT codes for overlapping services must comply with CPT guidelines and the policy’s clinical criteria to be eligible for coverage.

When billing multiple CPTs for related assays (for example 81243 + 81443), the member must meet the separate clinical criteria for each billed test (e.g., Fragile X criteria for 81243).
Do not duplicate billing for the same analytic content; follow CPT coding conventions for add-on and panel reporting.
If the laboratory reports multiple component results, include documentation that each billed procedure is distinct and medically necessary.

Billing Rule

Billing clarification for Fragile X

Billing clarification for Fragile X (FMR1) testing: if CPT 81243 (Fragile X) is billed along with a broader panel code such as 81443, the patient must meet the Fragile X–specific clinical criteria described in this policy (e.g., pregnancy or planning with relevant indications) even when Fragile X testing is performed concurrently with a panel.

Failure to meet Fragile X criteria when billing 81243 in addition to a panel may result in denial.
Document genetic counseling, indication (pregnancy/considering pregnancy), and any family history or clinical findings that support Fragile X testing.

Documentation Required

Pregnancy and relative documentation

When the member is pregnant or considering pregnancy, document pregnancy status and all relevant reproductive planning details. If testing is ordered because of a known familial variant, document the relationship and degree of relatedness (see 'Close relatives' definition) and provide the laboratory report or clinical note indicating the familial pathogenic/likely pathogenic variant.

Document whether the test is for the member or the reproductive partner and include partner follow-up plans.
Include genetic counseling notes and informed consent for carrier screening.
For familial variant testing, include pedigree or clear documentation of the affected relative and the identified variant details.

Note

Reference table and rationale update

Reference table and rationale updates have been made to reflect coding additions and criteria clarifications (for example adding CPT 81361 to basic panels and updating Policy Reference Table entries). Providers should consult the latest policy reference table for current test examples, CPT mappings, and rationale notes when preparing authorization requests and claims.

Policy Reference Table now includes updated examples for expanded and basic panels.
Rationale sections updated to reflect alignment with current ACOG/ACMG guidance and code additions.

Documentation Required

Partner / targeted follow-up

When a member is identified as a carrier, partner and targeted follow-up testing is recommended per ACMG/ACOG guidance: test the partner for the same gene(s) that have the identified pathogenic or likely pathogenic variant. Document counseling and plan for partner testing to support medical necessity.

Order partner testing targeted to the specific familial variant when a pathogenic/LP variant is identified in the member.
Do not routinely perform expanded panels on both partners in tandem; follow ACMG/ACOG recommendations for targeted partner follow-up.
Include documentation of counseling recommending partner follow-up and any results or plans.

DefinitionResidual risk is the remaining chance that an individual is a carrier despite a negative or normal carrier screening result; it varies by the test performed, the mutations included, and the patient’s ethnicity.

Practical impactA negative screen reduces but does not eliminate carrier status; counseling should include explanation of residual risk.

Dependence on panelResidual risk decreases as panels and variant sets increase in breadth and depth, but is not eliminated even with large panels.

Close relative

DefinitionClose relatives include first‑, second‑, and third‑degree relatives on the same side of the family: first‑degree (parents, siblings, children); second‑degree (grandparents, aunts/uncles, nieces/nephews, grandchildren, half‑siblings); third‑degree (great grandparents, great aunts/uncles, great grandchildren, first cousins).

Use in criteriaDocumentation should identify the degree of relationship when relying on a close relative’s known pathogenic/likely pathogenic variant for coverage of targeted testing.

Coverage implicationMany targeted carrier tests require a close relative with a known pathogenic/Likely pathogenic variant for medical necessity.

Tier 3 carrier screening

DefinitionTier 3 carrier screening (per ACMG) comprises genes with approximately ≥1/200 carrier frequency (includes Tier 1 and Tier 2) and is recommended to be offered to all pregnant patients and those planning pregnancy.

Tier frameworkACMG tiering: Tier 1 = CF + SMA + risk‑based; Tier 2 = ~1/100 carrier frequency or higher; Tier 3 = ~1/200 carrier frequency or higher (includes X‑linked); Tier 4 varies by lab and may be used for consanguinity or specific histories.

Clinical recommendationACMG recommends offering Tier 3 screening universally to pregnant and planning‑pregnancy patients; Tier 4 is reserved for consanguinity or relevant history.

Professional society guidance referenced

Referenced societiesAmerican College of Medical Genetics and Genomics (ACMG) guidance and technical standards are referenced for tiering and CFTR variant recommendations.

ACOGAmerican College of Obstetricians and Gynecologists (ACOG) practice bulletins and practice advisory on carrier screening and hemoglobinopathies are cited for universal offers (CF, SMA) and hemoglobinopathy screening.

Key actionable guidanceACMG and ACOG documents form the basis for updated testing criteria and nomenclature used in this policy (e.g., ACMG CFTR 100‑variant set and ACMG tier recommendations).