Association of clinical manifestations and immune alterations with genetic variants of uncertain significance in patients concerned for inborn errors of immunity.

Despite advances in genetic testing, Inborn Errors of Immunity (IEI) continue to present a diagnostic challenge, further complicated by genetic variants of uncertain significance (VUS). Therefore, this study evaluated associations of VUS with clinical and immunological characteristics in subjects with potential IEIs. Genes for which VUS were identified were clustered by distinct immune functions. Relationships between gene clusters and clinical and laboratory data were evaluated via SPSS and Python. Both unbiased clustering and manual method classified VUS into six distinct groups based on gene function. Clusters showed association with unique clinical and/or immunological profiles.