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:
GTGAAGGCTCATGGCAAGAAAGTGC [T>C] CGGTGCCTTTAGTGATGGCCTGGCT (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVPGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
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.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| 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
Publications / Origin
- 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
- 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
- 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