IthaID: 2571
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 109 CTG>CCG [Leu>Pro] | HGVS Name: | HBA1:c.329T>C |
| Hb Name: | Hb Milano | Protein Info: | α1 109(G16) Leu>Pro |
Context nucleotide sequence:
CTAAGCCACTGCCTGCTGGTGACCC [T>C] GGCCGCCCACCTCCCCGCCGAGT (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTPAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as:
Comments: Leu>Pro replacement at codon 109 is expected to alter the α1β1 contact, generating unstable α chains that undergo rapid proteolysis. No detection of abnormal haemoglobin by HPLC. Negative isopropanol stability test. Negative for HbH or Heinz inclusion bodies. Deduced as hyperunstable from low abundance. Pathogenicity predicted by in silico analysis. Reported as a heterozygote with mild microcytosis, and in association with an α-thal 3.7 kb (type I) deletion with marked microcythemia and mild anaemia.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
External Links
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | α-chain variant |
| Allele Phenotype: | α⁺ |
| Stability: | Hyperunstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 34363 |
| Size: | 1 bp |
| Located at: | α1 |
| 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 secondary structure |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Curcio C, Giannone V, Benzoni E, Cesaretti C, Ivaldi G, Hb Milano [α109(G16)Leu→Pro (CG>CG); : c.329T>C]: A Novel Variant on the α1-Globin Gene in an Italian Family., Hemoglobin, 43(1), 4-6, 2019