IthaID: 696
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 103 CAC>TAC [His>Tyr] | HGVS Name: | HBA2:c.310C>T |
| Hb Name: | Hb Lombard | Protein Info: | α2 103(G10) His>Tyr |
Context nucleotide sequence:
CCTCTTCTCTGCACAGCTCCTAAGC [C/T] ACTGCCTGCTGGTGACCCTGGCCGC (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSYCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as:
Comments: Mutation occurs at the site of an α1β1 contact. It disrupts binding to residues on the β chain, which disrupts α1β1 dimerization with subsequent accumulation of unstable free globin subunits. It also destabilizes free α chains by disrupting binding to the chaperone AHSP. It does not appear to have any haematological or clinical abnormalities.
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: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 34344 |
| Size: | 1 bp |
| Located at: | α2 |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Italian |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
HPLC
| ID | Hb Variant | Gene | Instrument | Method | Area (%) | Ret Time (min) | Comments | ||
|---|---|---|---|---|---|---|---|---|---|
| 165 | Hb Lombard | α2 | D-10 | Dual Kit Program | 0.5 | 2.55 | Heterozygous. Elutes as a shoulder in the descending part of the HbA peak. | [PDF] | |
| 166 | Hb Lombard | α2 | VARIANT | β-thal Short Program | 87 | 2.45 | Heterozygous. Elutes with HbA. | [PDF] | |
| 167 | Hb Lombard | α2 | VARIANT II | β-thal Short Program | 88.8 | 2.55 | Heterozygous. Elutes as a shoulder in the descending part of the HbA peak. | [PDF] | |
| 169 | Hb Lombard | α2 | VARIANT II | Dual Kit Program | 87.9 | 1.809 | Heterozygous. Elutes as a shoulder in the descending part of the HbA peak. | [PDF] |
In silico pathogenicity prediction
Publications / Origin
- Hoyer JD, McCormick DJ, Snow K, Kwon JH, Booth D, Duarte M, Grayson G, Kubik KS, Holmes MW, Fairbanks VF, Four new variants of the alpha2-globin gene without clinical or hematologic effects: Hb Park Ridge [alpha9(alpha7)Asn-->Lys (alpha2)], Hb Norton [alpha72(EF1)His-->Asp (alpha2)], Hb Lombard [alpha103(G10)His-->Tyr (alpha2)], and Hb San Antonio [A113(GH2)Leu-->Arg (A2)]., Hemoglobin , 26(2), 175-9, 2002
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013