CurrentCommunity Health Plan WashingtonPolicy N/A

V1.2025 Concert Genetic Testing: Metabolic, Endocrine, and Mitochondrial Disorders (PDF)

Defines medical necessity criteria for genetic testing (MTHFR variant analysis, monogenic diabetes/MODY panels, mitochondrial genome sequencing/deletion/duplication and nuclear gene testing, and other metabolic/endocrine/mitochondrial disorder testing) and lists covered conditions and coding examples. Provides background, references, and related policies.

Policy Summary

PayerCommunity Health Plan Washington

PolicyV1.2025 Concert Genetic Testing: Metabolic, Endocrine, and Mitochondrial Disorders (PDF)

Policy CodePolicy N/A

Change TypeRevisions to monogenic diabetes, MTHFR clarification, mitochondrial edits

Effective DateN/A

Next Review DateN/A

Key ActionDocument at least two listed clinical findings and completion of nondiagnostic conventional biochemical and additional indicated diagnostic testing when requesting mitochondrial testing; retain supporting documentation and submit prior authorization as required.

SourceLink

POLICY UPDATE CHANGES

Monogenic diabetes criteria revised (age thresholds and lab/clinical criteria updated) — culminated in V1.2025.

MTHFR targeted variant analysis (e.g., 677T, 1298C; CPT 81291) clarified as investigational for all indications.

Mitochondrial testing criteria and background edited for clarity (examples, tissue testing and methodology emphasis).

3Primary named policy sections with explicit coverage stances (MTHFR, Monogenic Diabetes, Mitochondrial Testing)

Coverage Summary

This policy (Concert genetic testing for metabolic, endocrine, and mitochondrial disorders) is CURRENT, last reviewed 11/2024, and is policy part 2 of 2. It contains 3 primary named policy sections with explicit coverage stances (MTHFR Variant Analysis; Monogenic Diabetes/MODY Panels; Mitochondrial Testing) and an overall coverage stance of mixed (some tests/panels are medically necessary when criteria are met; others are investigational).

High-level coverage summary: MTHFR targeted variant analysis (e.g., 677T, 1298C; CPT example 81291) is considered investigational for all indications. Multigene panels for monogenic diabetes (CPT examples 81403/81405/81406/81407/81479) and mitochondrial testing (CPT examples 81460/81465/81440/0417U) may be medically necessary when specific clinical criteria are met (see policy sections).

Age-related thresholds (policy testing triggers): • Neonatal/infant diabetes: testing medically necessary if diagnosis within first 12 months of life. • Young-onset diabetes: testing considered when diagnosis before 30 years of age with additional criteria (autoantibody negative and/or retained C‑peptide or family history consistent with autosomal dominant inheritance).

Key thresholds and metadata

Age for neonatal diabetes testingDiagnosis within first 12 months

Age for testing before adulthoodBefore 30 years

Date of Last Revision11/2024

Primary named sections3

Other covered disorders20+

Investigational tests listedMTHFR (81291)

Medical Necessity Criteria

Monogenic Diabetes (Including MODY) Panels - Investigational

Multigene panel analysis (81403, 81404, 81405, 81406, 81407, 81479) is investigational:

For all other indications not meeting the medically necessary criteria above

Mitochondrial Genome Sequencing, Deletion/Duplication, and/or Nuclear Genes - Investigational

Testing (81460, 81465, 81440) coverage stance:

Considered investigational for all other indications not meeting the medically necessary criteria above

Coding

MTHFR Variant Analysis - Example CPTCPTNot Covered

81291

MTHFR targeted variant analysis (example code listed as investigational)

Monogenic Diabetes / MODY Panels - Covered CPT (when criteria met)CPTCovered

81403	Multigene panel
81405	Multigene panel
81406	Multigene panel
81407	Multigene panel
81479	Unlisted molecular pathology procedure

Monogenic Diabetes - Additional codes referenced (investigational if not meeting criteria)CPT

81404

Multigene panel (listed in investigational set)

Mitochondrial Testing - Covered CPT/HCPCS (when criteria met)mixedCovered

81460	Mitochondrial genome sequencing
81465	Mitochondrial deletion/duplication testing
0417U	Nuclear genes / comprehensive mitochondrial analysis (example code)
81440	Nuclear-encoded mitochondrial gene panel

Other Covered Metabolic/Endocrine/Mitochondrial Disorder Codes - Example rangesCPTCovered

81400-81408	Comprehensive molecular panels range (examples)
81205	Single gene sequencing example
81250	Deletion/duplication of specific gene example

Mitochondrial Disorder ICD-10 ExamplesICD-10

E88.40	Mitochondrial disorder, unspecified
E88.41	Mitochondrial disorder, with specific manifestations
E88.42	Mitochondrial disorder
E88.49	Other mitochondrial disorders
G31.82	Leigh disease (example)
H49.811-H49.819	Ophthalmoplegia codes range (examples)

Monogenic Diabetes ICD-10 ExamplesICD-10

E10	Type 1 diabetes mellitus (used as example mapping)
E11	Type 2 diabetes mellitus (example mapping)
E16.1	Other hypoglycemia
E16.2	Hypoglycemia, unspecified

MTHFR ICD-10 Example mapping (informational only)ICD-10

E03.9	Hypothyroidism, unspecified (example mapping shown in doc)
E55.9	Vitamin D deficiency, unspecified (example mapping)
E72.12	Disorder of homocysteine metabolism (example mapping)
E78.2	Mixed hyperlipidemia (example mapping)
E78.5	Hyperlipidemia, unspecified (example mapping)
E88.9	Metabolic disorder, unspecified (example mapping)
O03	Spontaneous abortion (example mapping)
N96	Habitual aborter (example mapping)
R53.83	Other fatigue (example mapping)
Z00.00	Encounter for general adult medical examination (example mapping)

Provider Actions

Documentation Required

Document clinical features and prior diagnostic testing

Document at least two clinical features consistent with a metabolic, endocrine, or mitochondrial disorder and any prior nondiagnostic biochemical testing. Retain results of biochemical labs (e.g., metabolic panels, lactate, ammonia, plasma amino acids, urine organic acids, acylcarnitine profile, endocrine hormone levels) and any relevant imaging, muscle biopsy, or prior genetic test results to support medical necessity for genetic testing.

Affected CPT codes: 81460, 81465, 0417U, 81440

Prior Authorization

Prior authorization implied for panel testing

Multigene panels (including MODY/monogenic diabetes panels) and mitochondrial genome or nuclear mitochondrial gene panels are subject to medical necessity review and are likely to require prior authorization before testing. Contact the Health Plan or submit a prior authorization request per plan requirements prior to ordering testing when applicable.

Background and Evidence

Background: The policy provides clinical background on hereditary metabolic and endocrine disorders and on mitochondrial disorders as clinically heterogeneous conditions caused by mtDNA or nuclear gene mutations; genetic testing helps identify specific disorders to guide treatment and family screening.

MTHFR testing: MTHFR variants can alter homocysteine metabolism but do not change management for elevated homocysteine; professional guidance (ACMG) recommends against ordering MTHFR polymorphism testing for thrombophilia, recurrent pregnancy loss, or for at-risk relatives, and the policy lists MTHFR targeted variant analysis as investigational for all indications (examples: thrombophilia, pregnancy loss, pharmacogenetics).

Mitochondrial testing considerations and preferred methodologies: The Mitochondrial Medicine Society and GeneReviews endorse NGS of the full mtDNA genome as the preferred methodology rather than limited point-mutation testing; recognize that many pathogenic mtDNA variants are heteroplasmic and may be undetectable in blood, therefore recommend assessing mtDNA in another tissue (e.g., skeletal muscle or urine/urinary epithelium) when blood testing is negative or when tissue heteroplasmy is suspected. The policy specifically highlights heteroplasmy analysis in urine (e.g., for m.3243A>G/MELAS) and recommends comprehensive nuclear gene panels (NGS with complete coverage) or exome sequencing when indicated.

Source	Summary
ACMG MTHFR practice guideline
Recommendations against MTHFR polymorphism testing for thrombophilia or recurrent pregnancy loss; MTHFR genotyping should not be ordered for at-risk family members (ACMG 2013, confirmed 2020).
ADA guidance
Recommendations for genetic testing in neonatal diabetes and suspected MODY, including testing for infants with diabetes in first 6–12 months and testing those <30 years who are autoantibody negative and/or have retained C-peptide (ADA 2021; referenced consensus).
Mitochondrial Medicine Society consensus
Prefer NGS of the mtDNA genome; consider tissue testing and heteroplasmy analysis (urine), perform deletion/duplication testing and comprehensive nuclear gene NGS when indicated (Mitochondrial Medicine Society 2015).

Definitions (brief)

Mitochondrial diseaseHeterogeneous group of disorders caused by dysfunctional mitochondria responsible for oxidative phosphorylation.

Revision History

10/23revised

Monogenic diabetes criteria updated: age for diagnosis in I.A. changed from first 6 months to first 12 months; age threshold in I.B. changed from before 35 years to before 30 years; antibodies and C‑peptide language reworded and specific C‑peptide values removed; criteria wording for atypical type 2 diabetes replaced with 'diagnosis of diabetes not characteristic of type 1 or type 2 diabetes'; removal of requirement to include specific genes in panels.

01/24revised

Monogenic diabetes criteria reiterated/confirmed with same revisions: diagnosis within first 12 months (I.A.) and before 30 years (I.B.), antibody and C‑peptide criteria reworded, and panel requirements simplified.

04/24revised