So, we have modified this paragraph to introduce this information: “Only two variants (c.404+3A>G and c.705+3A>G) displayed 26% and 21% of the mgFL-transcript, respectively. Unfortunately, it is not known the minimal amount of RAD51C expression to confer tumor suppressor haplosufficiency so, these splicing assays were not considered informative (PVS1_O_N/A).” Note that leaky variants generate complex minigene read-outs (two or more transcripts), and are therefore classified accordingly (see methods).
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?