TY  - GEN
N2  - Individuals who inherit a pathogenic mutation in SDHA have an increased risk of cancer. However, there is often insufficient evidence to properly assess pathogenicity, and the majority of variants identified are variants of uncertain significance (VUS). Incorporating functional evidence can enhance the clinical interpretation of SDHA VUS, but the functional criteria for SDHA-variant cancer pathogenicity are not well defined. In this work, I developed novel models for the functional characterization of SDHA variants. I then investigated what consequences distinguish cancer from non-cancer variants. These insights allow us to determine which SDHA VUS have cancer-like dysfunction, improving our ability to identify patients with increased cancer risk. 
DO  - 10.6083/bpxhc42380
DO  - doi
AB  - Individuals who inherit a pathogenic mutation in SDHA have an increased risk of cancer. However, there is often insufficient evidence to properly assess pathogenicity, and the majority of variants identified are variants of uncertain significance (VUS). Incorporating functional evidence can enhance the clinical interpretation of SDHA VUS, but the functional criteria for SDHA-variant cancer pathogenicity are not well defined. In this work, I developed novel models for the functional characterization of SDHA variants. I then investigated what consequences distinguish cancer from non-cancer variants. These insights allow us to determine which SDHA VUS have cancer-like dysfunction, improving our ability to identify patients with increased cancer risk. 
AD  - Oregon Health and Science University
T1  - Novel models and methods for the functional characterization of disease relevant SDHA variants
ED  - Heinrich, Michael
ED  - Agarwal, Anupriya
ED  - McCullough, Amanda
ED  - O'Roak, Brian
ED  - Tyner, Jeffrey
ED  - Klug, Lillian
ED  - Khosroyani, Homma
ED  - Mentor
ED  - Committee chair
ED  - Committee member
ED  - Committee member
ED  - Committee member
ED  - Other
DA  - 2023-12-14
AU  - Kent, Jason
L1  - https://digitalcollections.ohsu.edu/record/42380/files/Kent.Jason.2023.pdf
PB  - Oregon Health and Science University
LA  - eng
PY  - 2023-12-14
ID  - 42380
L4  - https://digitalcollections.ohsu.edu/record/42380/files/Kent.Jason.2023.pdf
KW  - Succinate Dehydrogenase
KW  - Loss of Function Mutation
KW  - Genetics, Medical
KW  - sdha
KW  - vus
KW  - functional assay
KW  - succinate dehydrogenase
TI  - Novel models and methods for the functional characterization of disease relevant SDHA variants
Y1  - 2023-12-14
L2  - https://digitalcollections.ohsu.edu/record/42380/files/Kent.Jason.2023.pdf
LK  - https://digitalcollections.ohsu.edu/record/42380/files/Kent.Jason.2023.pdf
UR  - https://digitalcollections.ohsu.edu/record/42380/files/Kent.Jason.2023.pdf
ER  -