Hb Tacoma: G>T Or G>C, And Does It Matter?

Hb Tacoma [beta 30(B12)Arg -> Ser] is a missense variant that is caused by either an AGG>AGT or AGG>AGC substitution at codon 30 of the HBB gene. Currently, the latter is classified as a rare cause of beta(0)-thalassemia (beta(0)-thal). We propose that HBB: c.93G>C has been incorrectly assigned as beta(0)-thal and discuss whether HBB: c.93G>T or HBB: c.93G>C should be classified as beta(+)-thal instead, or as beta-globin variants without thalassemic effect. We present several subjects who are heterozygous for Hb Tacoma, one with HBB: c.93G>T and two with HBB: c.93G>C, to support our conclusions.