Saturation_Genome_Editing_of_RAD51C
We are performing a deep mutational scan at the RAD51C locus to functionally characterize the pathogenicity of variants at the nucleotide level. Specifically, we are employing Saturation Genome Editing (SGE) to edit endogenous RAD51C exons in the haploid, human cell line, HAP1.  RAD51C is one of the RAD51 paralogs and is involved in the Homology Directed Repair (HDR) pathway. Pathogenic variants in RAD51C have been associated with predisposition to both breast and ovarian cancer and there is also a suggestion that individuals carriers of disruptive variants in the gene may also develop other cancers such as gastric cancer. Additionally, individuals homozygous for pathogenic RAD51C alleles can develop Fanconi Anemia, which is associated with birth defects, bone marrow failure, and a risk of cancer. Importantly, of all the RAD51C variants available in ClinVar, >50% are classified as variants of uncertain significance (VUS); therefore, knowing their possible functional consequences would help their clinical interpretation.