CurrentCentenePolicy N/A

V1.2024 Concert Genetics Genetic Testing Hematologic Condition (non-cancerous)

Defines medical necessity criteria for genetic testing (targeted/familial variant analysis and gene/variant testing) for non-cancerous hematologic conditions, lists covered tests/genes, investigational indications, relevant CPT codes and related ICD-10 codes, and references policy cross-links and background evidence.

Policy Summary

PayerCentene

PolicyV1.2024 Concert Genetics Genetic Testing Hematologic Condition (non-cancerous)

Policy CodePolicy N/A

Change TypeRevised (title, coding, references, wording)

Effective Date

Next Review Date

Key ActionDocument that a close relative has a known pathogenic or likely pathogenic variant for targeted known familial variant analysis and follow Health Plan prior authorization processes when seeking coverage.

SourceLink

POLICY UPDATE CHANGES

Updated title to reflect V1.2024 version; overview, coding, reference-table, background and references updated; wording 'coverage criteria' replaced with 'criteria'.

Policy developed and approved 03/23; semi-annual review and update 10/23 with edits to test listings and wording.

9Example covered rare hematologic conditions listed

2Sections with investigational stance (G6PD, VWD)

~20Distinct CPT/HCPCS codes referenced

Coverage Summary

This policy defines medical necessity criteria for genetic testing (targeted/familial variant analysis and gene/variant testing) for non-cancerous hematologic conditions, lists covered tests/genes and CPT/HCPCS codes, describes investigational indications, and provides related documentation and coding guidance for providers. It is intended to guide coverage decisions for genetic testing used to confirm or establish diagnoses that may affect management and eliminate further diagnostic workup.

Policy context: Payer = health plans affiliated with Centene Corporation; Policy title = Concert Genetics: Genetic Testing for Hematologic (Non-cancerous) Conditions; Version = V1.2024; Status = CURRENT.

Policy metadata

PayerCentene

Policy TitleConcert Genetics: Genetic Testing for Hematologic (Non-cancerous) Conditions (V1.2024)

StatusCURRENT

Last review2023-10-01

Medical Necessity Criteria (by indication)

Known Familial Variant Analysis for Hematologic Conditions (Non-cancerous)

Targeted mutation analysis for a known familial variant is considered medically necessary when ALL of the following are met:

ALL of the following

Targeted mutation analysis for a known familial variant (CPT 81403, 81258, 81362)
The member/enrollee has a close relative with a known pathogenic or likely pathogenic variant causing the condition
Close relatives include first-, second-, and third-degree blood relatives on the same side of the family

Known Familial Variant Analysis - Investigational

Targeted mutation analysis for a known familial variant is considered investigational when the following is true:

ALL of the following

Coding

Targeted / Known Familial Variant Analysis CPTCPTCovered

81403	Targeted mutation analysis for known familial variant (example listed)
81258	Targeted mutation analysis (listed as known familial variant code in policy)
81362	Targeted mutation analysis (listed in policy)

Factor V and Factor II Variant Analysis CPTCPTCovered

81241	F5 (Factor V) variant analysis
81240	F2 (Prothrombin) variant analysis

Hemoglobinopathy CPTCPTCovered

81257	HBA1 deletion/duplication or variant analysis (alpha globin)
81259	HBA2 variant analysis or testing
81269	HBA1/HBA2 related testing (listed)
S3845	Alpha-thalassemia related (HCPCS miscellaneous CPT S code)
S3850	Alpha/beta globin test (S code listed)
81361	HBB sequencing analysis
81363	HBB deletion/duplication analysis (listed)
81364	HBB related testing
S3846	HBB related S code

Hemophilia CPTCPTCovered

81406	F8 full gene sequencing / variant analysis (listed)
81407	F8 related testing (listed)
81238	F9 sequencing/analysis
81479	Unlisted molecular pathology procedure (used for some F9 tests as listed)

G6PD CPTCPTExperimental

81247	G6PD targeted variant analysis
81248	G6PD testing (additional)
81249	G6PD full gene testing (listed)

von Willebrand / GP1BA / VWF CPTCPTExperimental

81401	GP1BA variant analysis
81403	Targeted variant analysis (also used elsewhere)
81404	VWF testing (sequencing)
81405	VWF related testing
81406	VWF/F8 listed code (overlap noted)
81408	VWF testing (listed)
81479	Unlisted molecular pathology procedure

Other Covered Hematologic Conditions RangeCPTCovered

81400-81408

Range of genomic sequencing / gene panel CPT codes referenced for other covered hematologic conditions

Common ICD-10 codes referencedICD-10

D68.51	Inherited thrombophilia (specific)
D68.2	Other thrombophilia
D68.59	Other hemorrhagic conditions
R79.1	Abnormal coagulation profile
Z86.2	Personal history of thrombophilia
I82.90	Pulmonary embolism without acute cor pulmonale, unspecified
D68.52	Prothrombin-related thrombophilia
D56.0	Alpha thalassemia
D56.9	Thalassemia, unspecified
D53.9	Hemolytic anemia, unspecified

1–10 of 24

1/3

Provider Actions & Billing Impact

Documentation Required

Document familial pathogenic variant for targeted testing

For targeted mutation analysis using CPT 81403, 81258, or 81362, document that a close relative has a known pathogenic or likely pathogenic variant causing the condition. Include identification of the affected relative per the policy definition of close relatives (first-, second-, or third-degree blood relatives on the same side of the family).

Affected codes: 81403, 81258, 81362
Definition of close relative per policy definitions

Prior Authorization

Prior authorization likely required per Health Plan rules

This clinical policy provides medical necessity guidance; providers must follow the Health Plan’s prior authorization and benefit administration processes when seeking coverage for genetic tests. Prior authorization is likely required per plan rules—follow your Health Plan’s PA and benefits process before ordering testing.

Background & Evidence

Rationale: Genetic testing can confirm diagnoses of non-cancerous hematologic disorders when clinical signs, symptoms, or laboratory screening are suggestive and when a confirmed genetic diagnosis would guide management or obviate additional diagnostic testing. The policy references expert guidance and technical standards — including ACMG technical standards for factor V Leiden and prothrombin testing, GeneReviews summaries for hemoglobinopathies and hemophilia, and specialty society guidance — to define appropriate indications for testing.

Referenced organizations and evidence sources include the American College of Medical Genetics and Genomics (ACMG), GeneReviews, the American College of Obstetricians and Gynecologists (ACOG), the Centers for Disease Control and Prevention / NHLBI, and the American Academy of Family Physicians (AAFP) among others; these sources inform the specific testing indications and recommended laboratory evaluation pathways.

The policy also notes that some conditions do not require genetic testing to establish the diagnosis: for example, G6PD deficiency can be diagnosed by quantitative spectrophotometric analysis or a rapid fluorescent spot test detecting NADPH generation, and von Willebrand disease is diagnosed using standard laboratory and biochemical testing rather than genetic testing as the primary diagnostic method.

Source	Notes
ACMG technical standard (Zhang 2018)
Supports testing indications for factor V Leiden and factor II c.*97G>A; testing recommended for first unprovoked VTE (especially <50 years), VTE at unusual sites, recurrent VTE, select family history and laboratory scenarios.
GeneReviews / Expert sources
Used as background for hemoglobinopathy and hemophilia testing recommendations; details diagnostic laboratory features and recommended mutation analysis use when biochemical testing is inconclusive or for genetic counseling/prenatal planning.

Definitions — Close relatives: First-, second-, and third-degree blood 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, and first cousins.

Revision History

03/23policy_development_approval

Policy developed and approved (policy developed and approval recorded 03/23); administrative and content clarifications with no change to core clinical coverage criteria.

10/01/2023semi_annual_review_updateLatest

Semi-annual review (10/23) with updates: title updated to V1.2024, overview, coding, reference-table, background and references updated; multiple coding and reference edits across hemoglobinopathy, hemophilia, G6PD, and von Willebrand sections (e.g., added GeneDx and ARUP references; adjusted listed test types); wording 'coverage criteria' replaced with 'criteria'.

Policy Summary

PayerCentene

PolicyV1.2024 Concert Genetics Genetic Testing Hematologic Condition (non-cancerous)

Policy CodePolicy N/A

Change TypeRevised (title, coding, references, wording)

Effective Date

Next Review Date

SourceLink

On This Page

Indication is other than having a close relative with a known pathogenic or likely pathogenic variant (i.e., all other indications)

Factor V Leiden (F5) and Prothrombin (F2) Variant Analysis for Inherited Thrombophilia

F5 (CPT 81241) and F2 (CPT 81240) variant analysis to confirm or establish diagnosis is considered medically necessary when ANY of the following are met:

Member meets at least one of

A first unprovoked venous thromboembolism (VTE) younger than 50 years old
VTE at unusual sites (e.g., hepatic portal, mesenteric, cerebral veins)
Recurrent VTE
Personal history of VTE with at least one of
- Two or more family members with a history of VTE
- One first-degree relative with VTE at a young age
Low activated protein C (APC) resistance activity
Female under age 50 who smokes and has history of acute myocardial infarction
First-degree relative known to be homozygous for factor V Leiden or factor II c.*97G>A
Pregnancy/estrogen-related scenario
- Asymptomatic pregnant female or female contemplating pregnancy with a first-degree relative with unprovoked VTE or VTE provoked by pregnancy or contraceptive use
- Pregnant female or female contemplating pregnancy or estrogen use who has a first-degree relative with a history of VTE AND the member/enrollee is a known carrier for factor V Leiden and/or factor II c.97*G>A variant
Pregnant female or female contemplating pregnancy with a previous non-estrogen-related VTE or VTE provoked by a minor risk factor

Factor V/II - Investigational

F5 (81241) and F2 (81240) variant analysis is considered investigational for:

ANY of the following

All other indications not listed as medically necessary
Fetal loss or adverse pregnancy outcomes (examples: placental abruption, fetal growth restriction, preeclampsia)

HBA1/HBA2 and/or HBB Variant Analysis (Hemoglobinopathies)

HBA1/HBA2 variant analysis (CPT 81257, 81259, 81269, S3845, S3850) and/or HBB variant analysis (CPT 81361, 81363, 81364, S3846) is medically necessary when ANY of the following are met:

ANY of the following

Member's hematologic screening results (examples: MCV, MCH, CBC, hemoglobin electrophoresis, DCIP) are positive for a hemoglobinopathy
Member's hematologic screening results do not conclusively diagnose or rule out a hemoglobinopathy
Examples: MCV, MCH, CBC, hemoglobin electrophoresis, dichlorophenol indophenol (DCIP)

HBA/HBB - Investigational

HBA1/HBA2 and/or HBB variant analysis is considered investigational for:

ALL of the following

All other indications not specified above

F8 and/or F9 Variant Analysis (Hemophilia A/B)

F8 variant analysis (CPT 81403, 81406, 81407) and/or F9 variant analysis (CPT 81238, 81479) is medically necessary when ALL of the following OR specific feature sets are present:

Either clinical features OR laboratory features

Clinical features (any of)
- Hemarthrosis (especially with mild or no antecedent trauma)
- Deep-muscle hematomas
- Intracranial bleeding in the absence of major trauma
- Neonatal cephalohematoma or intracranial bleeding
- Prolonged oozing or renewed bleeding after initial bleeding stops following tooth extractions, mouth injury, or circumcision
- Prolonged, delayed bleeding, or poor wound healing following surgery or trauma
- Unexplained GI bleeding or hematuria
- Heavy or prolonged menstrual bleeding (especially with onset at menarche)
- Prolonged nosebleeds, especially recurrent and bilateral
- Excessive bruising (especially with firm, subcutaneous hematomas)
Laboratory features (all of)
- Normal platelet count
- Prolonged activated partial thromboplastin time (aPTT)
- Normal prothrombin time (PT)

F8/F9 - Investigational

F8 and/or F9 variant analysis is considered investigational for:

ALL of the following

All other indications not listed as medically necessary

G6PD Variant Analysis

G6PD variant analysis (CPT 81247, 81248, 81249) coverage stance:

ALL of the following

G6PD variant analysis to confirm or establish a diagnosis of G6PD deficiency is considered investigational
Genetic testing not required for diagnosis per policy
Note: Diagnosis of G6PD deficiency can be achieved by quantitative spectrophotometric analysis or rapid fluorescent spot test detecting NADPH from NADP

GP1BA and/or VWF Variant Analysis (von Willebrand Disease)

GP1BA and/or VWF variant analysis (CPT 81401, 81403, 81404, 81405, 81406, 81408, 81479) coverage stance:

ALL of the following

Variant analysis to confirm or establish a diagnosis of von Willebrand disease is considered investigational
Genetic testing not recommended as primary diagnostic method per policy
Note: Diagnosis of von Willebrand disease can be achieved by standard laboratory and biochemical testing

Follow Health Plan PA process

Documentation Required

Clinical and laboratory evidence required for hemoglobinopathy testing

For HBA1/HBA2 and/or HBB variant analysis (e.g., CPT 81257, 81259, 81269, 81361, 81363, 81364), document the member’s hematologic screening results. Acceptable documented screening findings include positive or inconclusive results from tests such as MCV, MCH, CBC, hemoglobin electrophoresis, or DCIP.

Examples: MCV, MCH, CBC, hemoglobin electrophoresis, DCIP

Documentation Required

Clinical/lab features required for hemophilia testing

For F8 and/or F9 variant analysis (CPT 81403, 81406, 81407, 81238, 81479), document relevant clinical bleeding features and/or laboratory findings supportive of hemophilia. Clinical features include hemarthrosis, deep-muscle hematomas, intracranial bleeding without major trauma, prolonged or recurrent bleeding (including surgical or mucosal bleeding), heavy or prolonged menses, recurrent nosebleeds, or excessive bruising. Laboratory features to document include a normal platelet count, prolonged aPTT, and normal PT.

Affected codes: 81403, 81406, 81407, 81238, 81479

Denial Risk

Tests considered investigational risk denial

Genetic testing for G6PD (CPT 81247, 81248, 81249) and for GP1BA/VWF (CPT 81401, 81404, 81405, 81408, 81479, and related codes) is considered investigational per the policy. Claims for these genetic tests carry a risk of denial unless the testing falls under another covered criterion or is approved by a plan exception.

81247
81248
81249
81401
81404
81405
81408
81479