IthaID: 922

Names and Sequences

Functionality: Globin gene causative mutation Pathogenicity: Pathogenic / Likely Pathogenic
Common Name: CD 35 TAC>TTC [Tyr>Phe] HGVS Name: HBB:c.107A>T
Hb Name: Hb Philly Protein Info: β 35(C1) Tyr>Phe

Context nucleotide sequence:

Protein sequence:

Also known as:

Comments: The phenylalanine substitution results in the loss of the normal hydrogen bond between the tyrosine hydroxyl group β35 and the carboxyl group of aspartic acid α126 at the α1β1 contact. Alteration of the α1β1 interface favours the formation of monomers with subsequent accumulation of free globin subunits. Positive heinz body test and increased heat precipitability of the haemoglobin (Hb). No abnormal Hb detected by electrophoresis or column chromatography; phenylalanine is an almost perfect isomorphous replacement of tyrosine.

We follow the HGVS sequence variant nomenclature and IUPAC standards.


Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: β-chain variant
Allele Phenotype:N/A
Stability: Unstable
Oxygen Affinity: Increased Oxygen Affinity
Associated Phenotypes: Haemolytic anaemia [HP:0001878]


Chromosome: 11
Locus: NG_000007.3
Locus Location: 70831
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: French, German, Italian
Molecular mechanism: Altered α1β1 interface
Inheritance: Recessive
DNA Sequence Determined: Yes

In silico pathogenicity prediction

Sequence Viewer

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Publications / Origin

  1. Rieder RF, Oski FA, Clegg JB, Hemoglobin Philly (beta 35 tyrosine phenylalanine): studies in the molecular pathology of hemoglobin., The Journal of clinical investigation, 48(9), 1627-42, 1969 PubMed
  2. Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013 PubMed
Created on 2010-06-16 16:13:16, Last reviewed on 2019-06-19 13:14:54 (Show full history)

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