Multiple sequence alignment demonstrating phylogenetic conservation of the three biologically characterized phosphorylated BRCA2 residues affected by missense variants of unknown clinical significance.

<p>Multiple sequence alignment demonstrating phylogenetic conservation of the three biologically characterized phosphorylated BRCA2 residues affected by missense variants of unknown clinical significance.</p

NetworKIN analysis of VUS affecting biologically uncharacterized phosphorylation sites in BRCA1 and BRCA2.

<p>In <b>bold</b> are BRCA1 mutations that fall within an experimentally identified but biologically uncharacterized phosphorylation site. ^aThe position and change at the amino acids specified by the missense variant is as reported in the BIC database. ^bThe nucleotide change conforms to the HGVS nomenclature. ^cSNP IDs correspond to the dbSNP database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062468#pone.0062468-Sherry1" target="_blank">[73]</a> SNP identifiers. ^dFrequency represents the number of times reported in the BIC database. ^eThe ten-residue long biologically uncharacterized kinase recognition motifs are shown. The biologically uncharacterized Serine (S), and threonine (T) residues shown to be phosphorylated by NetworKIN are underlined. * Sites that retained a score but was considered to be “abolished” due to score falling below 5 with the presence of the VUS.</p

Figure 1

<p><b>a.</b> Summary of phosphorylation sites studied in BRCA1. Residues in green represent <i>in vivo</i> phosphorylation sites have been biologically characterized in the literature. Residues in red represent <i>in vivo</i> phosphorylation sites identified via throughput methods where biological functions have not yet been determined. <b>b.</b> Summary of phosphorylation sites studied in BRCA2. Residues in green represent <i>in vivo</i> phosphorylation sites that have been biologically characterized in the literature. Residues in red represent <i>in vivo</i> phosphorylation sites identified via throughput methods where biological functions have not yet been determined.</p

NetworKIN analysis of BIC VUSs affecting biologically characterized phosphorylation motifs in BRCA1 and BRCA2.

<p>In <b>bold</b> are BRCA1 mutations that directly mutate an experimentally identified phosphorylation site. ^aThe position and change at the amino acids specified by the missense variant is as reported in the BIC database. ^bThe nucleotide change conforms to the HGVS nomenclature. ^cSNP IDs correspond to the dbSNP database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062468#pone.0062468-Sherry1" target="_blank">[73]</a> SNP identifiers. ^dFrequency represents the number of times reported in the BIC database. ^eThe ten-residue long biologically uncharacterized kinase recognition motifs are shown. The biologically uncharacterized Serine (S), and threonine (T) residues shown to be phosphorylated by NetworKIN are underlined.</p