IthaID: 2976
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 64 GGC>GTC [Gly>Val] | HGVS Name: | HBB:c.194G>T |
| Hb Name: | Hb Calgary | Protein Info: | β 64(E8) Gly>Val |
Context nucleotide sequence:
CAACCCTAAGGTGAAGGCTCATG [G/T] CAAGAAAGTGCTCGGTGCCTTTA (Strand: +)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHVKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: Found as de novo mutation, in two unrelated cases in early infancy, presented with severe transfusion-dependent haemolytic anaemia and severe dyserythropoiesis. The variant was hyperunstable and was not isolated on Hb electrophoresis. According to the American College of Medical Genetics and Genomics (ACMG) variant interpretation guideline, was classified as highly likely pathogenic.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Thalassaemia and Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-thalassaemia, β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | Hyperunstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70918 |
| 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: | Canadian, Pakistani |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Henderson SJ, Timbs AT, McCarthy J, Gallienne AE, Proven M, Rugless MJ, Lopez H, Eglinton J, Dziedzic D, Beardsall M, Khalil MS, Old JM, Ten Years of Routine α- and β-Globin Gene Sequencing in UK Hemoglobinopathy Referrals Reveals 60 Novel Mutations., Hemoglobin , 40(2), 75-84, 2016
- Martin G, Grimholt RM, Le D, Bechensteen AG, Klingenberg O, Fjeld B, Fourie T, Perrier R, Proven M, Henderson SJ, Roy NBA, Hb Calgary (: c.194G>T): A Highly Unstable Hemoglobin Variant with a β-Thalassemia Major Phenotype., Hemoglobin, 45(4), 215-219, 2021