IthaID: 690
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Benign / Likely Benign |
|---|---|---|---|
| Common Name: | CD 99 AAG>GAG [Lys>Glu] | HGVS Name: | NM_000558.5(HBA1):c.298A>G |
| Hb Name: | Hb Turriff | Protein Info: | α1 99(G6) Lys>Glu |
Context nucleotide sequence:
GCTTCGGGTGGACCCGGTCAACTTC [A/G] AGGTGAGCGGCGGGCCGGGAGCGAT (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFELLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as: Hb Turriff-I
Comments: The lysine residue at α99(G6) is in the central cavity of the haemoglobin tetramer, situated in the region of the α1β1 contact. The Lys>Glu replacement does not appear to impair β-chain interactions. It disrupts AHSP binding, hence variant may be mildly destabilizing. Initially reported as a de novo mutation (α1 or α2) in a Scottish person during HbA1c screening (22% of the total Hb). Reported as an α1 globin gene mutation in a Japanese person with a high HbA1 level, hence called Hb Turriff-I (10.5% of the total Hb). Variant was not associated with any haematological disturbance. Normal isopropanol stability test.
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: | 37994 |
| Size: | 1 bp |
| Located at: | α1 |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Scottish, Japanese |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Langdown JV, Davidson RJ, Williamson D, A new alpha chain variant, Hb Turriff [alpha 99(G6)Lys----Glu]: the interference of abnormal hemoglobins in Hb A1c determination., Hemoglobin , 16(1), 11-7, 1992
- Harano T, Harano K, Hong YF, Than AM, Suetsugu Y, Ohba K, The mutation of Hb Turriff [alpha99(G6)Lys --> Glu (AAG --> GAG)] is carried by the alpha1-globin gene in a Japanese (Hb Turriff-I)., Hemoglobin, 27(2), 123-7, 2003
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013