What Is a Variant of Uncertain Significance in Genetic Testing?

Genetic testing is a critical tool in the medical management of disease; however, for variants of uncertain significance there is insufficient evidence to prove a connection between the variant and disease and they should not be used as a basis for clinical decisions.

Inherited TP53 Variants and Risk of Prostate Cancer.

Background: Inherited germline TP53 pathogenic and likely pathogenic variants (gTP53) cause autosomal dominant multicancer predisposition including Li-Fraumeni syndrome (LFS). However, there is no known association of prostate cancer with gTP53.

Objective: To determine whether gTP53 predisposes to prostate cancer.

Inherited DNA-repair gene mutations in African American men with prostate cancer.

African American men with prostate cancer are understudied relative to Caucasians with prostate cancer with regard to testing for pathogenic germline DNA repair gene mutations. Herein we evaluate these two populations in a large commercial dataset and compare the detection of pathogenic/likely pathogenic alterations in 14 well annotated DNA repair genes (BRCA2, BRCA1, PALB2, ATM, RAD51C, CHEK2, PMS2, BARD1, BRIP1, MLH1, MSH2, MSH6, NBN, and RAD51D). Overall, pathogenic or likely pathogenic alterations in these 14 DNA repair genes were less likely to be detected in African Americans as compared to Caucasians.

Prevalence of Germline Variants in Prostate Cancer and Implications for Current Genetic Testing Guidelines.

Importance: Prostate cancer is the third leading cause of cancer-related death in men in the United States. Although serious, most of these diagnoses are not terminal. Inherited risk for prostate cancer is associated with aggressive disease and poorer outcomes, indicating a critical need for increased genetic screening to identify disease-causing variants that can pinpoint individuals at increased risk for metastatic castration-resistant prostate cancer.