Investigating rare genetic variants of unknown significance in LDHA

Abstract

The exponential expansion and advancement of genetic sequencing has revealed the molecular basis of many genetic diseases. However, many genetic mutations are still classified as variants of unknown significance (VUS). Our lab focused on eleven missense variants in Lactate Dehydrogenase A (LDHA), an enzyme vital in anaerobic respiration. The intent with our research is to produce data on the kinetic functionality of wild type LDHA and compare this to its mutants of unknown significance. This data, supplemented with the structural information of the mutants can help reduce the ambiguity in the diagnosis of genetic disorders involving the LDHA enzyme. Currently, we have recorded the baseline kinetic function of the wild type LDHA based on its ability to convert the coenzyme NADH to NAD+. While we have a general understanding of the kinetic function of our mutant variants, A320T, T309P, L190F, E55K, D46V, P139L, G282R, K119R, T95M, G103E, and I94F, further tests need to be conducted to reduce variability.