BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. BRAF mutations are present in approximately 50% to 60% of cutaneous melanomas and are also present at lower frequencies in other melanoma subtypes. The G469R variant accounts for less than 1% of mutations overall in melanoma; however, it has been shown to account for 13% of non-V600E BRAF mutations in a study of advanced melanoma cases. The G469R mutation results in an amino acid substitution at position 469 in BRAF and occurs within the highly conserved motif of the kinase domain. Amino acid substitutions at this positon have been shown to retain variable levels of kinase activity compared to the normal BRAF. The effect of this mutation (p.G469R) on the kinase activity of BRAF is unknown. Correlation with other clinical and lab findings is recommended.
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