Are Germline Mosaic TSC1/2 Variants Present in Controls? Implications for Diagnosis.

•We found that 100 control individuals without tuberous sclerosis complex did not have pathogenic or likely pathogenic heterozygous or mosaic TSC1/TSC2 variants. Six individuals had variants of unknown significance or likely benign variants. This finding will inform variant interpretation and clinical implications. •Detection of a mosaic TSC1/TSC2 variant with a low variant allele frequency of 3% or more, with pathogenic or likely pathogenic in silico findings, is likely to be clinically significant if an individual has features of TSC.