IthaID: 3004
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 41 TTC>GTC [Phe>Val] | HGVS Name: | HBB:c.124T>G |
| Hb Name: | Hb Valme | Protein Info: | β 41(C7) Phe>Val |
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRVFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: Found as a heterozygote with normal clinical presentation. Residue 41 is involved in the binding of the bêta-globin chain with heme. In Hb Valme, although Phe > Val mutation does not change polarity because both are apolar amino acids, Phe in HbA acts as a spacer that stabilizes the heme group in the more inclined position, which it takes up in the tertiary oxy structure. Its replacement by Val makes it easier for the heme group to turn to its more upright position in the deoxy structure because Val is a smaller amino acid, lacking the phenolic ring. It changes oxygen-binding properties; nevertheless, it does not affect hemoglobin stability.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | Silent Hb |
| Stability: | N/A |
| Oxygen Affinity: | Decreased Oxygen Affinity |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70848 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Spanish |
| Molecular mechanism: | Altered heme pocket |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Benítez IC, Lameiro PC, Ropero P, De la Osa JJ, Fernández FG, Ortiz AM, Hemoglobin Valme HBB:c.124T>G: a new hemoglobin variant with diminished oxygen affinity causes interference in hemoglobin A1c measurement in an automated ion-exchange HPLC method., Clin. Chem. Lab. Med. , 53(9), e211-3, 2015