IthaID: 596
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Benign / Likely Benign |
|---|---|---|---|
| Common Name: | CD 68 AAC>AAA [Asn>Lys] | HGVS Name: | HBA2:c.207C>A |
| Hb Name: | Hb G-Philadelphia | Protein Info: | α2 68(E17) Asn>Lys |
Context nucleotide sequence:
AGAAGGTGGCCGACGCGCTGACCAA [C/A] GCCGTGGCGCACGTGGACGACATGC (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTKAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as: Hb D-Baltimore, Hb D-St. Louis, Hb D-Washington, Hb G-Azakouli, Hb G-Bristol, Hb G-Knoxville, Hb Stanleyville-I
Comments: Reported as a cod68 AAC>AAG change on a chromosome with a normal complement of two α globin genes (αGα/αα) and as a cod68 AAC>AAG change on a chromosome that carries the -α3.7 thalassaemia deletion (-αG/αα) [IthaID: 3973]. Increases in the levels of Hb G-Philadelphia are the result of a deletion of one or more α-globin gene(s): ~25% with four α genes (αGα/αα), ~35% with three α genes (-αG/αα), ~45% with two α genes (-αG/-α), and 100% with one α gene (-αG/--). Different α genotypes present with variable extends of microcytosis and hypochromia, and a decreased ratio of α/β chain synthesis.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | α-chain variant |
| Allele Phenotype: | N/A |
| Stability: | N/A |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 34099 |
| Size: | 1 bp |
| Located at: | α2 |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | African, Chinese, Italian |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
HPLC
| ID | Hb Variant | Gene | Instrument | Method | Area (%) | Ret Time (min) | Comments | ||
|---|---|---|---|---|---|---|---|---|---|
| 351 | Hb G-Philadelphia | α2 | D-10 | Dual Kit Program | 22.5 | 3.96 | Heterozygous. Associated with alpha thal. | [PDF] | |
| 254 | Hb G-Philadelphia | α2 | D-10 | Dual Kit Program | 30 | 3.92 | Heterozygous. Associated with alpha thal. | [PDF] | |
| 352 | Hb G-Philadelphia | α2 | VARIANT | β-thal Short Program | 21.7 | 4.04 | Heterozygous. Associated with alpha thal. | [PDF] | |
| 255 | Hb G-Philadelphia | α2 | VARIANT | β-thal Short Program | 26.7 | 4.01 | Heterozygous. Eluates as HbD. Associated with alpha thal. | [PDF] | |
| 354 | Hb G-Philadelphia | α2 | VARIANT II | Dual Kit Program | 23 | 3.37 | Heterozygous. Elutes as HbS. Associated with alpha thal. | [PDF] | |
| 353 | Hb G-Philadelphia | α2 | VARIANT II | β-thal Short Program | 21.5 | 4.13 | Heterozygous. Elutes as HbD. Associated with alpha thal. | [PDF] | |
| 257 | Hb G-Philadelphia | α2 | VARIANT II | Dual Kit Program | 28.9 | 3.35 | Heterozygous. Eluates as HbS. Associated with alpha thal. | [PDF] | |
| 256 | Hb G-Philadelphia | α2 | VARIANT II | β-thal Short Program | 29 | 4.12 | Heterozygous. Eluates as HbD. Associated with alpha thal. | [PDF] |
In silico pathogenicity prediction
Publications / Origin
- Bowman BH, Barnett DR, Hodgkinson KT, Schneider RG, Chemical characterization of haemoglobin G-St-I., Nature , 211(5055), 1305-6, 1966
- Blackwell RQ, Wang CL, Liu CS, Shih TB, Haemoglobin G Philadelphia, alpha68(alphaE17) Asn leads to Lys, in a Chinese subject in Taiwan., Vox Sang. , 25(2), 184-6, 1973
- Milner PF, Huisman TH, Studies of the proporation and synthesis of haemoblogin C Philadelphia in red cells of heterozygotes, a homozygote, and a heterozygote for both haemoglobin G and alpha thalassaemia., Br. J. Haematol. , 34(2), 207-20, 1976
- Molchanova TP, Pobedimskaya DD, Huisman TH, The differences in quantities of alpha 2- and alpha 1-globin gene variants in heterozygotes., Br. J. Haematol. , 88(2), 300-6, 1994
- Molchanova TP, Pobedimskaya DD, Ye Z, Huisman TH, Two different mutations in codon 68 are observed in Hb G-Philadelphia heterozygotes., Am. J. Hematol. , 45(4), 345-6, 1994
- Khalil MS, Timbs A, Henderson S, Schuh A, Hussein MR, Old J, Haemoglobin (Hb) G-Philadelphia, Hb Stanleyville-II, Hb G-Norfolk, Hb Matsue-Oki and Hb Mizushi can form a panel of α-chain variants that overlap in their phenotype: the novel use of StyI to screen for Hb G-Philadelphia., Int J Lab Hematol, 33(3), 318-25, 2011