ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.300T>A (p.Asp100Glu)

dbSNP: rs34013622
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
Unidade de Eritropatologia e Metabolismo do Ferro, Centro Hospitalar e Universitário de Coimbra RCV001175128 SCV001251649 pathogenic Erythrocytosis, familial, 6 2019-11-01 criteria provided, single submitter case-control The Asp100Glu variant in HBB is a high oxygen affinity hemoglobin described first in members of a Portuguese family. The altered functional properties of this variant likely result from the inability to form a hydrogen bond between beta-chain aa 100Glu and alpha-chain aa 43Tyr; such a bond is formed in deoxy Hb A between the normally occurring beta 100Asp and alpha 43Tyr. The affected members have a distinct erythrocytosis with high hemoglobin levels.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226436 SCV003922705 uncertain significance not specified 2023-03-22 criteria provided, single submitter clinical testing Variant summary: HBB c.300T>A (p.Asp100Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251404 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.300T>A, (also known as Asp99Glu or Hb Coimbra) is a known high oxygen affinity hemoglobin variant, and is reported in several heterozygotes, who were mostly asymptomatic and had compensatory erythrocytosis found in routine blood tests (e.g. Tamagnini_1991, Bento_2013, Oliveira_2018). To our knowledge, no homozygous occurrences or compound heterozygosity with pathogenic HBB variants were reported, therefore no clear conclusions about association of the variant with Hemoglobinopathy can be made. Publications reported experimental evidence evaluating samples from heterozygous carriers, and demonstrated that the variant resulted in an increase in oxygen affinity (Tamagnini_1991, Jorge_2018), but no differences in Bohr effect were found (Jorge_2018). One submitter has provided clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic for Erythrocytosis. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.