IthaID: 902
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 28 CTG>CAG [Leu>Gln] | HGVS Name: | HBB:c.86T>A |
| Hb Name: | Hb Saint Louis | Protein Info: | β 28(B10) Leu>Gln |
Context nucleotide sequence:
GTGGATGAAGTTGGTGGTGAGGCCC [T>A] GGGCAGGTTGGTATCAAGGTTACAA (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEAQGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: β28 Leu>Gln change produces an unstable haemoglobin, which gives rise to severe haemolytic anaemia associated with methaemoglobinaemia. The β28 (B10) Gln and the distal histidine (E7) swing towards each other, stabilizing a water molecule in the normally hydrophobic haem pocket which results in thermal instability and methaemoglobin formation [PMID: 1581206].
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | Methemoglobinaemia |
| Stability: | Unstable |
| Oxygen Affinity: | Increased Oxygen Affinity |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70680 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 1 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | N/A |
| Ethnic Origin: | French, Slovakian, Yugoslavian, Indian |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Cohen-Solal M, Seligmann M, Thillet J, Rosa J, Haemoglobin Saint Louis beta28 (B10) leucine leads to glutamine. A new unstable haemoglobin only present in a ferri form., FEBS letters, 33(1), 37-41, 1973
- Colah RB, Nadkarni A, Gorakshakar A, Sawant P, Gorivale M, Mehta P, Sawant M, Ghosh K, Five Rare β Globin Chain Hemoglobin Variants in India., Indian J Hematol Blood Transfus , 32(0), 282-6, 2016