IthaID: 3004

Names and Sequences

Functionality: Globin gene causative mutation Pathogenicity: Variant of Uncertain Significance
Common Name: CD 41 TTC>GTC [Phe>Val] HGVS Name: HBB:c.124T>G
Hb Name: Hb Valme Protein Info: β 41(C7) Phe>Val

Protein sequence:

Also known as:

Comments: Found as a heterozygote with normal clinical presentation. Residue 41 is involved in the binding of the bêta-globin chain with heme. In Hb Valme, although Phe > Val mutation does not change polarity because both are apolar amino acids, Phe in HbA acts as a spacer that stabilizes the heme group in the more inclined position, which it takes up in the tertiary oxy structure. Its replacement by Val makes it easier for the heme group to turn to its more upright position in the deoxy structure because Val is a smaller amino acid, lacking the phenolic ring. It changes oxygen-binding properties; nevertheless, it does not affect hemoglobin stability.

We follow the HGVS sequence variant nomenclature and IUPAC standards.

External Links


Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: β-chain variant
Allele Phenotype:Silent Hb
Stability: N/A
Oxygen Affinity: Decreased Oxygen Affinity
Associated Phenotypes: N/A


Chromosome: 11
Locus: NG_000007.3
Locus Location: 70848
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: Spanish
Molecular mechanism: Altered heme pocket
Inheritance: Recessive
DNA Sequence Determined: Yes

In silico pathogenicity prediction

Publications / Origin

  1. Benítez IC, Lameiro PC, Ropero P, De la Osa JJ, Fernández FG, Ortiz AM, Hemoglobin Valme HBB:c.124T>G: a new hemoglobin variant with diminished oxygen affinity causes interference in hemoglobin A1c measurement in an automated ion-exchange HPLC method., Clin. Chem. Lab. Med. , 53(9), e211-3, 2015
Created on 2016-08-24 10:59:40, Last reviewed on 2016-08-24 14:19:58 (Show full history)

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