Very important comment. As the reviewer indicates, it would be essential to define the threshold of RAD51C expression from which it keeps its tumor suppressor activity. Unfortunately, it is not known by now but this finding would provide critical information to determine the pathogenicity of leaky spliceogenic variants.
Lines 342-359 – This paragraph discusses two RAD51C variants, c.404+3A>G and c.705+3A>G, for which mg-FL transcripts were detected in 26.3% and 21.3% or transcripts, respectively. The discussion of these variants in this section (and in other sections) does not address the significance of canonical transcripts in these cases. Leaky splice variants have been reported in various genes and sometimes can be associated with milder phenotypes (or no phenotypes), presumably because the canonical isoforms contribute to a “phenotypic rescue”. Is it known whether there is a threshold of RAD51C deficiency that is tolerated before associated cancer risks become increased?