Testing of V455I STAT1 variant
Although extremely rare in the general population (MAF: 0,00006), the
variant (c.1363G>A, p.V455I) was classified as being likely
benign (Sift 0.19, Polyphen 0.115, CADD 28.3). As the performance of
those algorithms in the setting of GOF mutations is limited, we decided
to evaluate the functional impact of this novel variant. Total STAT1
levels in monocytes were determined by flow cytometry in the patient and
her family and were similar to that of healthy controls (Figure
3A) . Similarly, we did not observe any differences in terms of STAT1
phosphorylation after 15min of INF-γ stimulation (Figure 3B) .
In addition, family testing (Sanger sequencing) revealed that this
variant is inherited from the asymptomatic father (Figure 2B) ,
suggesting this variant not to be disease causing.