Genetic Testing for Hereditary Form

Medical Policy
Subject: Genetic Testing for Hereditary and Multifactorial Conditions
Applies To: Individual and Family Plan (IFP) Policy Number: MP-0227 Effective Date: January 2024 Revised: n/a Document Page Length: 6 Medicare will follow: LCD Molecular Pathology Procedures (L34519)
Medical Policy Statement: Genetic Testing for Hereditary and Multifactorial Conditions may be considered medically necessary when the clinical criteria described in this Policy are met. Definitions:
Genetic Counseling: Genetic counseling is the process of helping individuals understand and adapt to the medical, psychological, and familial indications of genetic contributions to disease. Genetic counseling services span the life cycle from preconception counseling to infertility evaluation, prenatal genetic screening and diagnosis, and include predisposition evaluation and genetic diagnosis. Genetic counseling may be necessary, both pre-and post-genetic test, to interpret family and medical histories to assess the chance of disease occurrence and recurrence, educate regarding inheritance, testing, management prevention and resources, and counsel to promote informed choices and adaptation to risk or condition.
Genetic Testing: Genetic testing involves the analysis of human deoxyribonucleic acid (DNA), ribonucleic acid (RNA), chromosomes, proteins, and certain metabolites in order to detect alterations or changes related to an inherited disorder. Germline Variant: When a pathogenic variant occurs in an egg or sperm it is referred to as a Germline Variant. Germline gene variants are inherited or passed down in families by blood relatives. Some conditions, such as sickle cell

disease, are caused by a single germline pathogenic variant. Other conditions, such as diabetes and heart disease, are more complex.
Global Developmental Delay: Is defined as significant delay in younger children, under age five years, in at least two of the major developmental domains: gross or fine motor; speech and language; cognition; social and personal development; and activities of daily living. Immediate – For the purpose of this policy, the term immediate means within 90 days. Moderate/Severe/Profound Intellectual Disability: Is defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, diagnosed by 18 years of age. Multifactorial Conditions: Inherited conditions that may also be caused by more than one germline pathogenic variant. The presence of a pathogenic variant(s) may increase an individual's risk of developing one of these conditions; however, a combination of genetic and environmental factors such as nutrition, exercise, weight, smoking, drinking alcohol, and medication use may influence the observable characteristics of the condition.
Description:
Certain types of genetic testing are used to identify germline pathogenic variant(s) that cause hereditary and multifactorial conditions. This testing may include single gene testing, targeted analysis, and multigene sequencing panels. Genetic testing may be used to aid in diagnosis or confirmation of a disorder in a symptomatic individual (i.e., diagnostic or confirmatory testing), to predict risk of future disease in an asymptomatic individual (i.e., predictive testing), to allow reproductive planning (i.e., reproductive carrier testing), prenatal testing of a fetus, preimplantation genetic diagnosis, and newborn screening. The scope of this policy includes diagnostic and confirmatory, single or multigene testing for hereditary and multifactorial conditions.
Clinical Criteria: (Indications/Limitations)

1. Prior Authorization is Required:

   A. Genetic Testing require HFHP prior authorization to review the medical necessity of each gene within a test or a panel. B. Prior authorization is required for each genetic testing specific CPT code. C. Testing will be considered only for the number of genes or tests necessary. D. Multiple stacked CPT codes billing from laboratories will not be approved.

2. General Coverage Guidance: Genetic testing for Hereditary and Multifactorial Conditions may be considered medically necessary when ALL the following conditions are met:
   A. Actionable Use: The results of the testing will immediately directly impact clinical decision making.
   B. Treating Physician: Ordered only by the treating physician involved in the management of the member's cancer.
   C. Technical and clinical validity: The test must be accurate, sensitive and specific, based on sufficient, quality scientific evidence to support the claims of the test.
3. Genetic Counselling: Pre and Post test genetic counselling may be medically necessary to assist members to understand and adapt to the medical, psychological, and familial indications of genetic contributions to disease.

4. Single Gene Genetic Testing for Germline Conditions:
   A. Single gene germline genetic testing may be performed to diagnose or confirm the presence of a disease causing pathogenic or likely pathogenic variant and may be appropriate if an individual demonstrates characteristics of a genetically-linked heritable disease or has a direct risk factor for the development of the specific disease in question. Single gene genetic testing may be considered medically necessary for the following conditions: i. Alpha-1 antitrypsin disease
   ii. Alpha and beta thalassemia
   iii. Canavan disease
   iv. Cystic fibrosis
   v. DFNB1 nonsyndromic hearing loss and deafness
   vi. Familial hypercholesterolemia (homozygous and heterozygous)
   vii. Fragile X syndrome viii. Gaucher disease ix. Muscular dystrophies (DMD, BMD, EDMD, DM1, DM2, SM) x. Niemann-Pick disease xi. Nuclear mitochondrial genes xii. Rett syndrome xiii. Sickle cell disease

   xiv. Tay-Sachs disease xv. 21- hydroxylase deficiency

5. Multi-Gene Genetic Testing Panels (Germline Genetic Testing Panels) Overall, the clinical utility of genetic testing is dependent upon the particular phenotype or observable characteristics of a disease, and set of genes being tested. Similar to genetic testing for single genes, smaller, more targeted panels to assess for a particular disorder may have clinical utility when used to aid in diagnosis of heterogeneous genetic conditions. A. Multigene Panel Testing for Nonsyndromic Hearing Loss may be necessary when all the following criteria are met:
   i. individual lacks physical findings suggestive of a known genetic syndrome ii. medical and birth histories are not suggestive of an environmental (i.e., non-genetic) cause of hearing loss, including but not limited to: a. otitis media b. tympanic membrane perforation c. temporal bone fractures d. auditory tumors e. congenital rubella f. congenital syphilis g. congenital toxoplasmosis h. congenital malformations of the inner ear i. congenital cytomegalovirus (CMV) infection j. prematurity B. Multigene Panel Testing in Global Developmental Delay and Intellectual Disability is considered medically necessary when EITHER of the following criteria is met: i. Member is diagnosed with global developmental delay following formal assessment by a developmental pediatrician or neurologist ii. Member is diagnosed with moderate/severe/profound intellectual disability following formal assessment by a developmental pediatrician or neurologist iii. And ALL the following are met: a. The test has been shown to improve clinical outcomes b. results will directly impact clinical decision-making and clinical outcome for the individual being tested c. presence of genetic variant(s) is highly predictive for the development of the multifactorial condition

6. Newborn Screening Newborn screening is performed shortly after birth for genetic disorders (e.g., screening for metabolic, endocrine, hemoglobin and other disorders).
   Member coverage for genetic newborn screening testing is considered medically necessary in accordance with state mandates. Limitations:

   1. Genetic screening in the general population is considered not medically necessary.