Extended Data Fig. 3: Functional consequence and in silico discordance of SAMD9/9 L mutations.
Representative Western blot showing the protein levels 24 h after transfection with plasmid expressing SAMD9 wildtype (WT), SAMD9 n = 5 patient mutations (left), and SAMD9L wildtype (WT) with SAMD9L n = 5 patient mutations (right). The mock control was HEK293 transfected with empty vector. (b) Effect of co-occurring germline and second-site (somatic) SAMD9/9Lmut on HEK293 cell proliferation when expressed either alone or in cis from single constructs. Mean ± SEM from n = 3 independent experiments performed in triplicate are presented. P-values using paired t-test are shown for each double mutant in comparison to the respective germline SAMD9/9Lmut. (c) Comparative evaluation of pathogenicity of 49 germline SAMD9/9L mutations by CADD prediction and HEK293 growth assay.
