Two cases of mosaic germline SVA insertions in SMARCB1: implications for rhabdoid tumour predisposition diagnosis.

Rhabdoid tumour predisposition syndrome (RTPS) is a highly penetrant cancer predisposition syndrome caused by germline variants in SMARCB1 or less frequently in SMARCA4. Genetic testing for this syndrome involves sequence and deletion/duplication analysis of these two genes. Standard clinical testing is limited in detecting structural variants. Here we describe two patients who tested negative on standard clinical germline panel testing for RTPS but were each found to have a mosaic germline insertion of an SVA (SINE-VNTR-Alu) element in the SMARCB1 gene by more advanced comprehensive genomic analysis. These two cases demonstrate the importance of structural variants and broader genomic sequencing for individuals suspected of having an underlying germline cancer predisposition syndrome, such as RTPS.