ClinVar

Description

The Hb Chico variant (HBB: c.200A>C; p.Lys67Thr, also known as Lys66Thr when numbered from the mature protein rs35939489) has been reported in individuals with mild anemia (HbVar database and references therein). Functional characterizations indicate that Hb Chico has reduced oxygen affinity and might be mildly unstable (Bonaventura 1991, HbVar and references therein). However, the phenotype of this variant in the presence of other alpha globin variants is unknown. This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, other amino acid substitutions at this codon (Lys67Asn, Lys67Ile, Lys67Glu) have been reported in heterozygous individuals with mild to moderate anemia and are considered disease causing (HbVar and references therein). The lysine at residue 66 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.838). Based on available information, this variant is considered to be likely pathogenic. References: Link to HbVar database for Hb Chico: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=367 Link to HbVar database for Hb Ulm: https://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=1191&.cgifields=histD Link to HbVar database for Hb Vigo: https://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=3136&.cgifields=histD Link to HbVar database for Hb I-Toulouse: https://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=366&.cgifields=histD Bonaventura J et al. (1991) Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66----Thr) and its isolated beta chains. J Biol Chem. 266(34):23033-40.