IthaID: 1181
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 111 GTC>GCC [Val>Ala] | HGVS Name: | HBB:c.335T>C |
| Hb Name: | Hb Stanmore | Protein Info: | β 111(G13) Val>Ala |
Context nucleotide sequence:
CCACAGCTCCTGGGCAACGTGCTGG [C/T] CTGTGTGCTGGCCCATCACTTTGGC (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLACVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: Described as an unstable haemoglobin (Hb) with reduced oxygen affinity in a double heterozygote with β0-thalassaemia. Alteration of the α1β1 interface, favouring the formation of monomers with subsequent accumulation of free globin subunits. The change in side chain at β111 possibly disturbs the α1β1 contact at the adjacent site, β112 (G14). Positive heinz body test and increased isopropanol precipitability of the Hb. Detection of abnormal Hb variant by reversed-phase HPLC.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | Unstable |
| Oxygen Affinity: | Decreased Oxygen Affinity |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71909 |
| 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: | Italian, Japanese |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Como PF, Wylie BR, Trent RJ, Bruce D, Volpato F, Wilkinson T, Kronenberg H, Holland RA, Tibben EA, A new unstable and low oxygen affinity hemoglobin variant: Hb Stanmore [beta 111(G13)Val----Ala], Hemoglobin, 15(1), 53-65, 1991
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013