GxVISION® Hereditary Cancer Risk Assessment

American College of Obstetrics & Gynecology

ACOG Committee Opinion Number 634, June 2015

A hereditary cancer risk assessment is the key to identifying patients and families who may be at increased risk of developing certain types of cancer.

If a hereditary cancer risk assessment suggests an increased risk of a hereditary cancer syndrome, referral to a specialist in cancer genetics or a health care provider with expertise in genetics is recommended for expanded gathering of family history information, risk assessment, education, and counseling, which may lead to genetic testing.

American College of Medical Genetics & Genomics, ACMGG Practice Guidelines (doi:10.1038/gim.2014.147)

Hereditary breast–ovarian cancer (HBOC) syndrome is caused by mutations in BRCA1 and BRCA2 genes and is characterized by increased risks for early-onset breast, multiple breast primaries, male breast, and epithelial ovarian, Fallopian tube, or primary peritoneal cancers.

Cancers of the pancreas, prostate, and melanoma are more common in individuals with HBOC syndrome.

The pathology of “triple-negative phenotype” breast cancer (estrogen receptor–negative, progesterone receptor–negative, and HER2/neu–negative) has been strongly associated with BRCA1 mutations.

The likelihood of identifying a BRCA1/2 mutation in a woman with ovarian cancer at any age is around 13–18%.

Of males with breast cancer, 15–20% has a BRCA1/2 mutation.

The overall prevalence of BRCA1 mutations is estimated at 1 in 300. BRCA2 mutations are estimated at 1 in 800. Founder mutations in populations e.g., Ashkenazi Jewish, Icelandic, and Mexican Hispanic populations lead to increased mutation prevalence in these populations.

NCCN, Version 2.2021- November 20, 2020

Genetic testing should be considered for appropriate high-risk individuals where it will impact medical management of the tested individual and/or their at-risk family members.

The probability of a mutation being detected based on these criteria will vary depending family structure.
Individuals with unknown or limited family history, such as fewer than 2 female first- or second-degree relatives having lived beyond 45 years in either lineage, may have an underestimated probability of familial mutation detection.

The likelihood of detecting a mutation may be very low in families with a large number of unaffected female relatives.

Patients who have received an allogeneic bone marrow transplant should not have molecular genetic testing with current technologies using blood samples due to unreliable test results from contamination by donor DNA. DNA extracted from a fibroblast culture can be used. If not available, then a buccal sample can be considered with understanding of the risk of donor DNA contamination.

Variant classification is based on a Mendelian perspective and employs the recommended five-tier classification system recommended by the American College of Medical Genetics, ACMGG.

A sequence change can be classified as:

Positive – Pathogenic Variant(s) Detected

This result means that a mutation or a genetic change that increases the lifetime chance of developing certain cancers was identified. This variant directly contributes to the risk of developing cancer. Some pathogenic variants may not be fully penetrant. In the case of recessive conditions, a single pathogenic variant may not be sufficient to cause disease on its own. Additional evidence is not expected to alter the classification of this variant. The final report contains detailed risk information specific to the mutation(s). This result does not mean that the patient has cancer or will definitely develop cancer in their lifetime. Follow up with physicians, healthcare providers and genetic counseling is recommended.

Likely Pathogenic Variants(s) Detected

The result means that a mutation or a genetic change that is likely to increase the lifetime chance of developing certain cancers was identified. However current scientific evidence is insufficient to prove this conclusively. Additional evidence is expected to confirm this assertion of pathogenicity, but we cannot fully rule out the possibility that new evidence may demonstrate that this variant has little or no clinical significance. The final report contains detailed risk information specific to the mutation identified. This result does not mean that the patient has cancer or will definitely develop cancer in their lifetime. Follow up with physicians, healthcare providers and genetic counseling is recommended.

Variant(s) of Uncertain Significance (VUS) Detected

Variant(s) of Uncertain Significance (VUS) are variants that do not fit into pathogenic, likely pathogenic, or benign classifications according to ACMGG and/or other relevant Professional standards, or the criteria for pathogenic or likely pathogenic and benign are contradictory for the variant. There is not enough information or conflict information at this time to support a more definitive classification of this variant on cancer risk.

Negative – No Reportable Variant(s) Detected

The result means that no pathogenic, likely pathogenic (LP) or variant of uncertain significance (VUS) were detected. Likely benign and benign variants are not included in the report and are available upon request.

Test Inconclusive or Test Failed

Test evaluation was inconclusive. Possible reasons are not enough DNA present in test specimen or the specimen failed quality assurance measures. A new specimen submission is recommended.

Variant Information Available

All variant information is available upon request. Vairants classified as benign and likely benign are not reported. Variants not detected by the performed assay may impact the phenotype.

Otogenetics is committed to working with patients to ensure that everyone has access to testing without financial burden.

• Medicaid patients will NOT have patient out of pocket responsibility.
• We treat all out-of-network claims as if they are in-network.
• We will work with all insurers (primary and secondary policies) to maximize your qualified coverage.

Otogenetics testing service is covered by many insurance plans, the exact amount your patients  owe may vary based on their individual plan and financial situation.

Here is our commitment to your patients regarding costs:

• We will reach out to your patient if we estimate their cost could be more than $50 (the average out of pocket Otogenetics patients pay).
• We will discuss the estimate with your patients, and review their affordability.

Your patient may receive information from their insurer, known as an Explanation of Benefits (EOB), regarding the test they received from Otogenetics.

An EOB from your patient’s insurer is NOT A BILL.

A bill for the test(s) provided by Otogenetics comes ONLY from Otogenetics.

If there is any patient out of pocket cost after Otogenetics has exhausted all options for reimbursement coverage and financial assistance, Otogenetics will reach out to your patient.