Improving Medical Diagnoses By Linking Genetic Variation To Clinical Data

Research Question:

Determine if Variants of Uncertain Significance (VUS) in medically relevant genes (e.g. ACMG59) can be reclassified as pathogenic variants, by linking individuals’ genetic VUS information to clinical data.

Value / Impact:

1. It is important to eliminate the number of VUSs so that definitive and tailored treatment plans can be made for individuals with VUS mutations in medical relevant genes.

2. In the Low-Density Lipoprotein Receptor (LDLR) case study, our objective is to determine which of VUSs are associated with high cholesterol or heart disease. If high cholesterol or heart disease is detected in individuals possessing these VUSs, it increases the likelihood that these particular VUS are pathogenic variants. If the variants are associated with low or normal cholesterol levels, they will be more likely to be benign. In the case of BRCA1 and BRCA2, the two genes most commonly associated with causing cancer, linkage to clinical data may validate laboratory tests that reveals the particular VUS to be a pathogenic variant, which will help to improve variation annotation pipelines.

3. To conclude, linkage to clinical data will eliminate the number of VUS so that more precise medical diagnosis can be made for patients of Asian ancestry.