IthaID: 230
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 106 CTG>CGG [Leu>Arg] | HGVS Name: | HBB:c.320T>G |
| Hb Name: | Hb Terre Haute | Protein Info: | β 106(G8) Leu>Arg |
Context nucleotide sequence:
CCTCTTATCTTCCTCCCACAGCTCC [A/C/G/T] GGGCAACGTGCTGGTCTGTGTGCTG (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLRGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: Leu>Arg substitution at position β106 (G8) associated with disruption of the heme pocket and heme loss. Presented with a severe Heinz body haemolytic anaemia and globin chain imbalance. Reported in a heterozygous state in a family with a severe, dominantly inherited β-thalassemia phenotype. Extremely unstable variant; its identity could only be studied by biosynthetic analysis in which a radio-active abnormal peak was observed. Isopropanol and heat stability tests were inconclusive [PMID: 429365, 447835].
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Thalassaemia and Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-thalassaemia, β-chain variant |
| Allele Phenotype: | Thalassaemia dominant Dominant |
| Stability: | Hyperunstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: |
Haemolytic anaemia [HP:0001878] Ineffective erythropoiesis [HP:0010972] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71894 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | North European, French |
| Molecular mechanism: | Altered heme pocket |
| Inheritance: | Dominant |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Adams JG, Steinberg MH, Boxer LA, Baehner RL, Forget BG, Tsistrakis GA, The structure of hemoglobin Indianapolis [beta112(G14) arginine]. An unstable variant detectable only by isotopic labeling., The Journal of biological chemistry, 254(9), 3479-82, 1979
- Adams JG, Boxer LA, Baehner RL, Forget BG, Tsistrakis GA, Steinberg MH, Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia., J. Clin. Invest., 63(5), 931-8, 1979
- Coleman MB, Steinberg MH, Adams JG, Hemoglobin Terre Haute arginine beta 106. A posthumous correction to the original structure of hemoglobin Indianapolis., The Journal of biological chemistry, 266(9), 5798-800, 1991
- Girodon E, Ghanem N, Vidaud M, Riou J, Martin J, Galactéros F, Goossens M, Rapid molecular characterization of mutations leading to unstable hemoglobin beta-chain variants., Annals of hematology, 65(4), 188-92, 1992
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013