ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.200A>C (p.Lys67Thr)

dbSNP: rs35939489
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811148 SCV000603899 likely pathogenic not provided 2021-05-18 criteria provided, single submitter clinical testing 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.
OMIM RCV000016299 SCV000036567 other HEMOGLOBIN CHICO 2017-12-12 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.