This policy governs the use of broad and targeted genetic tests — including single‑gene sequencing and deletion/duplication, disorder‑specific multigene panels, chromosomal microarray (CMA), mitochondrial genome sequencing (mtDNA) with deletion/duplication analysis, and exome/genome sequencing (standard and rapid) — to establish or confirm diagnoses for suspected multisystem inherited genetic disorders in Community Health Plan Washington members. It applies when the clinician documents a clinical indication consistent with a listed disorder and follows the disorder‑specific diagnostic thresholds and prior‑testing guidance in the criteria sections. The policy also provides example billing/coding references and describes expectations for documentation, prior authorization where applicable, and recommended testing methodologies for specific scenarios (for example, NGS of the mtDNA genome and tissue selection when heteroplasmy is suspected).

Eligibility for testing is determined by disorder‑specific clinical criteria summarized in this policy. Where a condition‑specific node exists (for example, Marfan/FBN1, TSC1/TSC2, NF1, NF2, PIK3CA, CHD7, Noonan/RASopathies, Angelman/Prader‑Willi, and mitochondrial disorders), the member must meet the listed clinical diagnostic thresholds or documented family history triggers described in that node to qualify for coverage. Providers should reference the relevant disorder section for the precise clinical features, numeric thresholds, and any required prior testing or stepwise evaluation.

For Neurofibromatosis type 1 (NF1), testing of the proband is considered medically necessary when the individual meets diagnostic criteria or when a biological parent meets diagnostic criteria for NF1. The policy specifies that parental diagnosis is established when the parent has two or more NF1 diagnostic features; documentation of the parent’s clinical features should be included to support testing in the offspring.

A biological parent who meets the diagnostic criteria for NF1 creates a clear indication for genetic testing of the proband. In such cases, documentation that the parent fulfills the NF1 feature count (e.g., café au lait macules, neurofibromas, freckling, optic glioma, Lisch nodules, or a distinctive osseous lesion) should accompany the testing request.

Where specific disorder sections exist, eligibility follows those disorder‑specific rules. For example, connective tissue disorder panels are covered when the enrollee meets clinical criteria for Marfan, Loeys‑Dietz, classical Ehlers‑Danlos, or vascular EDS; COL3A1 testing follows vEDS major/minor criteria; and FBN1 testing follows Marfan diagnostic thresholds. Consult each disorder node for the exact combinations of features required to qualify for testing.

Other disorder‑specific eligibility examples provided elsewhere in the policy include tiered and molecular testing pathways for Beckwith‑Wiedemann and Silver‑Russell syndromes, and the major/minor feature thresholds for Tuberous Sclerosis Complex (TSC) that trigger TSC1/TSC2 sequencing and deletion/duplication. These sections define the clinical triggers that must be documented to support coverage.

For Neurofibromatosis type 2 (NF2), the policy includes specific adult and pediatric diagnostic findings that trigger consideration of sequencing or related testing. Adult criteria were operationalized to include features such as bilateral vestibular schwannomas, unilateral vestibular schwannoma with additional tumor/cataract findings, or multiple meningiomas with defined accompanying features; tumor tissue identification of an NF2 pathogenic variant is also listed as an indication to pursue germline testing. See the NF2 criteria node for full detail.

Where family history or known familial variant criteria previously appeared, some elements were consolidated or moved to the general approach policy for known familial variants. Providers should therefore follow the disorder‑specific node and the referenced general approach guidance when ordering testing for relatives or known familial variants. Documentation of the family history (three‑generation pedigree) is expected when relevant.

Mitochondrial testing eligibility requires both compatible clinical features and completion of preliminary diagnostic studies. The policy specifies that conventional biochemical testing (plasma/CSF lactic acid, ketones, plasma acylcarnitines, and urinary organic acids) and other indicated diagnostic evaluations must be completed and nondiagnostic before mtDNA genome sequencing or nuclear mitochondrial gene panels are considered. Tissue selection and heteroplasmy considerations (e.g., urine or muscle testing when blood is negative) are required elements of the clinical rationale.

For imprinting disorders such as Angelman and Prader‑Willi syndromes, the policy endorses a stepwise testing strategy: begin with methylation analysis of the 15q11‑q13 region; if normal, proceed to deletion analysis, then uniparental disomy testing, and finally imprinting‑center defect analysis as indicated. Age‑specific clinical features are used to determine when testing is appropriate. Documentation of the clinical features and the sequential testing performed should be provided.

Before pursuing high‑cost broad testing such as exome (ES) or genome sequencing (GS), the policy recommends that clinicians rule out alternate etiologies and perform appropriate prior evaluations (for example, focused clinical, biochemical, or radiologic workup) when feasible. For many conditions a tiered approach is recommended (panels or targeted testing first when phenotype suggests a single gene; ES/GS for heterogeneous or unexplained multisystem presentations), and prior ES reanalysis may be considered before proceeding to WGS. Documentation that prior evaluations were completed and nondiagnostic should be included with authorization requests.

Mitochondrial testing eligibility nodes reiterate that mtDNA testing should follow the Mitochondrial Medicine Society and GeneReviews guidance: use NGS of the complete mtDNA genome as the preferred methodology, and when blood testing is negative but clinical suspicion persists, perform mtDNA testing on another tissue (e.g., urine or muscle) because of tissue‑specific heteroplasmy. Nuclear gene NGS panels with complete coverage are preferred when primary mitochondrial disease is likely; whole exome sequencing may be considered if panels are non‑diagnostic.

The policy emphasizes selecting single‑gene testing versus broad panels based on phenotype. When clinical findings strongly suggest a single, commonly implicated gene (for example, PTPN11 in classic Noonan syndrome or characteristic NF1 features), single‑gene testing may be reasonable as an initial step; conversely, when phenotype is nonspecific or genetically heterogeneous, a multigene panel or exome/genome testing is preferred. The applicable disorder‑specific node indicates the preferred approach.

The policy defines Exome Sequencing (ES) as sequencing of the protein‑coding regions of the genome and Genome Sequencing (GS) as sequencing of the complete DNA sequence, including non‑coding regions; it also notes limitations to ES reanalysis when prior data are incompatible with current platforms or pipelines. These definitions and limitations should inform ordering decisions and expectations for reanalysis.

This document is a consolidated policy that incorporated criteria from several prior Concert genetic testing policies; revisions were made to clarify disorder‑specific criteria, remove certain minimum gene lists, update coding references, and add mitochondrial testing criteria. The policy is subject to regular review and has undergone recent semi‑annual updates; providers should use the most current policy version and follow plan‑level administrative procedures for coverage determinations.

Providers ordering genetic testing are expected to facilitate informed decision‑making through pre‑test and post‑test genetic counseling, to document the clinical indication and relevant family history (typically a three‑generation pedigree), and to record the patient’s preferences regarding secondary findings. For many disorder‑specific tests, the clinical features and numeric thresholds that justify testing must be documented in the medical record and provided as part of any prior authorization request.

The policy states that multigene panels for isolated hypermobility or hypermobile Ehlers‑Danlos syndrome (hEDS) are not supported; similarly, autism spectrum disorder/intellectual disability multigene panels are considered unsupported or have insufficient evidence for routine use. Providers should not order panel testing for these isolated presentations unless specific disorder criteria elsewhere in the policy are met.

Sequencing and/or deletion/duplication analysis of TSC1/TSC2, NF1, or NF2 is not covered when the member does not meet the specified diagnostic clinical criteria listed in the corresponding policy sections (for example, TSC major/minor feature thresholds, NF1 diagnostic feature counts, or the NF2 adult/pediatric tumor combinations). Requests lacking documentation that the diagnostic criteria are met may be denied.

Autism Spectrum Disorder/Intellectual Disability multigene panels are not supported by current evidence for routine use; national society guidance recommends CMA, Fragile X testing, and consideration of ES/GS rather than routine ASD/ID panel testing. Such panels should not be ordered for indications beyond those specified in guidelines.

PIK3CA testing is focused on PIK3CA‑Related Overgrowth Spectrum (PROS) presentations and is intended for typical, usually sporadic, PROS phenotypes. The policy specifies that PROS is typically a single occurrence in a family and that testing excludes familial syndromic forms; documentation of the affected tissue(s) and relevant imaging findings is expected due to common mosaicism. Deletion/duplication testing for PIK3CA was removed from the criteria because such events are uncommon.

During revisions the policy removed and replaced certain legacy example tests and CPT/PLA examples that were included in error and updated policy reference‑table entries. Some CPT examples were edited or removed from specific sections; providers should rely on the updated coding table and the payer’s billing guidance rather than legacy code listings.

As part of the consolidation and update process, some specific tests and example entries were removed from the policy reference tables or reassigned to other Concert policies. Providers should verify test availability and coding against the current policy reference table and the laboratory’s billing instructions. Items removed from coverage lists in this revision are noted in the policy references.

Genetic testing for multisystem inherited disorders requires matching the testing modality to the clinical scenario: targeted single‑gene or deletion/duplication testing when a specific phenotype is strongly suspected; multigene panels for phenotype groups with overlapping genes; CMA as a first‑tier test for DD/ID/ASD or multiple congenital anomalies; and mtDNA genome NGS with tissue‑specific testing when mitochondrial disease is suspected. The rationale is to maximize diagnostic yield while limiting unnecessary or low‑value testing and to ensure appropriate specimen selection (e.g., urine or muscle for mtDNA heteroplasmy).

The NF2 adult diagnostic criteria were clarified to operationalize triggers for testing — specifically, coverage is tied to findings such as bilateral vestibular schwannomas, unilateral vestibular schwannoma accompanied by at least two additional listed tumor/cataract findings, or multiple meningiomas with specified accompanying features (including age‑related cataract criteria). These explicit adult clinical triggers inform when NF2 sequencing or panel testing is considered medically necessary.

The revision process included coding and CPT/PLA updates: several example test entries and CPT/PLA mentions were edited or replaced in the policy reference tables to correct prior errors and align example codes with current test offerings. Providers should consult the policy’s coding sections and the payer’s billing guidance for up‑to‑date code usage rather than relying on earlier code mentions.

During consolidation some conditions and specific testing items were moved out of this policy and into other Concert policies, and certain items were removed from the coverage lists to avoid duplication or because they are better addressed elsewhere (for example, some rare conditions and specific example tests). The policy’s references and revision notes document these edits; providers should follow the current policy structure and cross‑reference related Concert policies where indicated.