CPT 81479, 81599, 84999 -single nucleotide variant

Coding    Code Description CPT

81479 Unlisted molecular pathology procedure

81599 Unlisted multianalyte assay with algorithmic analysis

84999 Unlisted chemistry procedure



Introduction

A “single nucleotide variant” (SNV) is a change in a specific section of a person’s DNA. These changes may increase a person’s risk of developing breast cancer. Medical studies have not shown that doing genetic tests to look at these SNVs is effective and reliable in predicting a person’s chance of getting breast cancer. For this reason, testing for one or more SNVs to predict a person’s risk of getting breast cancer is considered unproven (investigational).

Note:   The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a service may be covered.


Testing Investigational

One or more single nucleotide variants (SNVs)

Testing for one or more single nucleotide variants (SNVs) to predict an individual’s risk of breast cancer is considered investigational.
BREVAGenplus® The BREVAGenplus® breast cancer risk test is considered investigational for all indications, including but not limited to use as a method of estimating an individual patient’s risk for developing breast cancer.

Note: BRCA genetic testing should be used in those from high-risk families (see Related Policies).





Related Information 

Genetic Counseling

Experts recommend formal genetic counseling for patients who are at risk for inherited disorders and who wish to undergo genetic testing. Interpreting the results of genetic tests and understanding risk factors can be difficult for some patients. Genetic counseling helps individuals understand the impact of genetic testing,  including the possible effects the test results could have on the individual or their family members. It should be noted that genetic  counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Further, genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.

Evidence Review 

Description

A number of single nucleotide variants (SNVs), which are single base-pair variations in the DNA sequence of the genome, have been found to be associated with breast cancer and are common in the population but confer only small increases in the risk of getting breast cancer. Commercially available assays test for several SNVs to predict an individual’s risk of breast cancer relative to the general population. Some of these incorporate clinical information into risk prediction algorithms. The intent of this type of test is to identify subjects at increased risk who may benefit from more intensive surveillance.

Background

Gene Variants And Breast Cancer Risk

Rare, single-gene variants conferring a high risk of breast cancer have been linked to hereditary breast cancer syndromes. Examples are mutations in BRCA1 and BRCA2. These, and a few others, account for less than 25% of inherited breast cancer. Moderate risk alleles, such as variants in the CHEK2 gene, are also relatively rare and apparently explain very little of the genetic risk.

In contrast, several common SNVs associated with breast cancer have been identified primarily through genome-wide association studies (GWAS) of very large case-control populations. These alleles occur with high frequency in the general population, although the increased breast cancer risk associated with each is very small relative to the general population risk. Some have suggested that these common-risk SNVs could be combined for individualized risk prediction either alone or in combination with traditional predictors. Personalized breast cancer screening programs could then vary by the starting age and intensity of screening according to the person’s risk. Along these lines, the American Cancer Society recommends that women at high risk (>20% lifetime risk) should undergo breast magnetic resonance imaging (MRI) and a mammogram every year, and those at moderately increased risk (15%-20% lifetime risk) should  talk with their doctors about the benefits and limitations of adding MRI screening to their yearly mammogram.


Clinical Genetic Tests
BREVAGenplus®

BREVAGenplus® (Phenogen Sciences, Charlotte, NC) evaluates breast cancer-associated SNVs identified in GWAS. The first-generation test, BREVAGen, included 7 SNVs. In a 2015 report, the test included over 70 susceptibility SNVs.

Risk is calculated by combining individual SNV risks with the Gail model risk. BREVAGenplus® has been evaluated for use in African-American, white, and Hispanic patient samples age 35 years and older. BREVAGenplus® does not detect known high-risk mutations (eg, in BRCA). According to the BREVAGenplus® website, the test is not applicable to women who are already at high risk of breast cancer including those that have a personal or extensive family history of breast and/or ovarian cancer, LCIS [lobular carcinoma in situ], DCIS [ductal carcinoma in situ], AH [atypical hyperplasia] or have had prior thoracic RT [radiotherapy] under age 30. Any women with these risk factors are already at increased risk of breast cancer and should be screened and followed as such.Genetic Testing for Rett Syndrome