Outcomes of multigene panel testing for hereditary cancer in two Israeli medical centers 2013–2024

Purpose Multigene panel testing (MGPT) enables simultaneous detection of germline pathogenic/likely pathogenic variants (P/LP SV) in cancer susceptibility genes (CSG). The utility of MGPT in Israel, where most individuals eligible for oncogenetic testing undergo first-pass genotyping for predominant PVs in the BRCA1, BRCA2, MSH2, and MSH6 genes, has not been reported. Methods Individuals who underwent MGPT after oncogenetic counseling between October 2013 and December 2024 were eligible for participation in this ethically approved study. NGS genotyping of 29–160 genes was performed using commercial or in-house platforms. Clinical data were obtained from records. Results Among 2990 individuals, 145 pathogenic sequence variants were detected in 43 genes in 245 individuals (8.3%). Recurring PSVs in BRCA1, BRCA2, CHEK2, ATM, MSH2, and MSH6 were noted. CHEK2 (c.592+3A>T), PMS2 (c.943C>T), and CDKN2A (c.176T>G) were identified as potentially recurring founder variants. Conclusions The yield of MGPT in Israel, after exclusion of predominant founder PSVs, was modest. The identification of recurring PSVs warrants further investigation and potential inclusion in updated first-pass genotyping schemes.