IthaID: 1028

Names and Sequences

Functionality: Globin gene causative mutation Pathogenicity: Variant of Uncertain Significance
Common Name: CD 68 CTC>CCC [Leu>Pro] HGVS Name: HBB:c.206T>C
Hb Name: Hb Mizuho Protein Info: β 68(E12) Leu>Pro

Context nucleotide sequence:

Protein sequence:

Also known as:

Comments: Unstable variant associated with severe hemolytic anemia in early childhood. It also exhibits slightly increased oxygen affinity. Although P50 values are uninformative, hemolysate exhibits a biphasic behavior at very low saturation values on the Hill plot, consistent with a high oxygen-affinity Hb exhibiting reduced cooperativity, and present in relatively small quantity [PMID: 2272836]. The insertion of a prolyl in the place of the leucyl residue at the β68 position (E12) in the middle of the Ε-helix disrupts the helix, thus affecting the tertiary structure of the β subunits. This position is next to the β67 (E11) valyl residue, which has an important hydrophobic contact with the heme moiety near the distal histine β63 (E7), thus the β68 Leu>Pro substitution may disturb the heme pocket.

We follow the HGVS sequence variant nomenclature and IUPAC standards.


Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: β-chain variant
Allele Phenotype:N/A
Stability: Unstable
Oxygen Affinity: N/A
Associated Phenotypes: N/A


Chromosome: 11
Locus: NG_000007.3
Locus Location: 70930
Size: 1 bp
Located at: β
Specific Location: Exon 2

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: N/A
Ethnic Origin: Caucasian | Dutch | Italian | Japanese
Molecular mechanism: Altered secondary structure
Inheritance: Dominant
DNA Sequence Determined: Yes

In silico pathogenicity prediction

Sequence Viewer

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Publications / Origin

  1. Ohba Y, Miyaji T, Matsuoka M, Sugiyama K, Suzuki T, Sugiura T, Hemoglobin Mizuho or beta 68 (E 12) leucine leads to proline, a new unstable variant associated with severe hemolytic anemia., Hemoglobin, 1(5), 467-77, 1977 PubMed
  2. Labotka RJ, Vida LN, Honig GR, Hb Mizuho [beta 68(E12)Leu----Pro]. Second occurrence identified in a Caucasian child with hemolytic anemia and dense erythrocyte inclusions., Hemoglobin, 14(2), 129-36, 1990 PubMed
  3. Keeling MM, Bertolone SJ, Baysal E, Gu YC, Cepreganova B, Wilson JB, Huisman TH, Hb Mizuho or alpha 2 beta (2)68(E12)Leu----Pro in a Caucasian boy with high levels of Hb F; identification by sequencing of amplified DNA., Hemoglobin, 15(6), 477-85, 1991 PubMed
Created on 2010-06-16 16:13:16, Last reviewed on 2023-02-22 16:55:59 (Show full history)

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