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Germline Testing Criteria Clinical Scenario

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Germline Testing Criteria Clinical Scenario

A 44-year old female patient walks into your office. She has no personal history of cancer. Her mother was diagnosed with Stage II breast cancer at age 63, and a somatic test revealed no mutation in BRCA1/2. Her maternal uncle was diagnosed with metastatic prostate cancer at age 68.

Does this patient meet guidelines for germline testing?

Yes! This patient meets NCCN Criteria for germline testing due to her family history. Her mother’s diagnosis and close relative with metastatic prostate cancer meet guidelines.1 Even though her mother received a tumor test that did not reveal a BRCA1/2 mutation, the patient may still have a hereditary cancer risk, and a germline test is the only way to know for sure if her cancer may be hereditary.

Absence of a BRCA1/2 mutation on tumor profiling does not negate the need for germline testing in cases where the patient’s personal and/or family history is suggestive of a germline BRCA1/2 mutation or other hereditary cancer syndromes. Moreover, a somatic gene panel may not include all the genes associated with a hereditary cancer risk.2 Additionally, there are differing criteria for how germline and somatic variants are classified as pathogenic, benign, or uncertain.3

There are also often limitations to tumor testing technology to be aware of in this setting. Tumor sequencing may not cover all relevant areas of the gene, deletion/duplication analysis may not be part of the tumor analysis, a germline mutation could be mosaic and not present in the tumor specimen, and in rare cases, the germline mutation may have reverted to wildtype in the tumor.

Myriad’s myRisk® can provide more insight into this patient’s current and future risk.

To learn more about BRCA testing, click here.



  1. NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Breast and Ovarian (Version 3.2019). Accessed Sept. 6, 2019.
  2. Mandelker D & Zhang L. The emerging significance of secondary germline testing in cancer genomics. J Pathol. 2018;244(5):610-615.
  3. Lee LA, et al. Annotation of sequence variants in cancer samples: Processes and pitfalls for routine assays in the clinical laboratory. J Mol Diag. 2015;17(4):339-51.