IthaID: 3368
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 54 GTT>ATT [Val>Ile] | HGVS Name: | HBB:c.163G>A |
| Hb Name: | Hb Askew | Protein Info: | β 54(D5) Val>Ile |
| Also known as: |
We follow the
HGVS sequence variant nomenclature
and
IUPAC standards.
Context nucleotide sequence:
TGGGGATCTGTCCACTCCTGATGCT [G/A] TTATGGGCAACCCTAAGGTGAAGG (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAIMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Comments: During antenatal screening, a sample with abnormal ce-HPLC findings and positive sickle solubility testing was analyzed by ESI-MS. Three variants were identified: Hb Stanleyville II (α78Asn>Lys), Hb S (β6Glu>Val), and a third β-chain variant showing a +14 Da mass shift. Tryptic digestion and low-energy CID localized the substitution to β54, consistent with either Val>Leu or Val>Ile. Subsequent hot electron capture dissociation (HECD) demonstrated the diagnostic z₆ -29 Da ion, confirming the substitution as β54Val>Ile (and not Leu). This was further validated using synthetic peptides. No DNA sequencing was performed; the nucleotide change was inferred from the confirmed amino acid substitution.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | N/A |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70887 |
| 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: | English |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | No |
In silico pathogenicity prediction
Sequence Viewer
Publications / Origin
- Williams JP, Creese AJ, Roper DR, Green BN, Cooper HJ, Hot electron capture dissociation distinguishes leucine from isoleucine in a novel hemoglobin variant, Hb Askew, beta54(D5)Val-->Ile., J. Am. Soc. Mass Spectrom., 20(9), 1707-13, 2009 PubMed