IthaID: 1076


Names and Sequences

Functionality: Globin gene causative mutation Pathogenicity: Variant of Uncertain Significance
Common Name: CD 82 AAG>AAC HGVS Name: HBB:c.249G>C
Hb Name: Hb Providence Protein Info: β 82(EF6) Lys>Asn

Context nucleotide sequence:
GCCTGGCTCACCTGGACAACCTCAA [G>C] GGCACCTTTGCCACACTGAGTGAGC (Strand: -)

Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLNGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Also known as:

Comments: Hb Providence occurs in the red cells in two forms; Hb Providence Asn (asparagine) and Hb Providence Asp (aspartic acid), the latter resulting from the post-translational deamidation of the substituted asparagine residue. The amino acid change occurs at the EF6 position of the β chains that is normally occupied by an invariant lysyl residue (β82 (EF6) Lys). This position normally serves as a binding site for 2,3-diphosphoglycerate (2,3-DPG) and chloride. The replacement of Lys by Asn or Asp reduces the net positive charge of this site, which causes a weakening in the interaction with 2,3-DPG and, in turn, stabilizes the T-state conformation and decreases hemoglobin affinity for oxygen. This occurs without a concomitant change in the degree of cooperativity. Hb Providence Asp is the faster abnormal Hb component as seen by electrophretic methods and column chromatography. The parial binding of 2,3-DPG to Hb Providence Asn limits the deamidation process, which results in the Asp form making about two thirds of the Hb Providence in the red cells of carriers. Reported as a β82 AAG>AAC change by bidirectional sequence analysis.

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Phenotype

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

Location

Chromosome: 11
Locus: NG_000007.3
Locus Location: 70973
Size: 1 bp
Located at: β
Specific Location: Exon 2

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: N/A
Ethnic Origin: Japanese | African
Molecular mechanism: Altered 2,3-DPG binding site
Inheritance: Dominant
DNA Sequence Determined: Yes

HPLC

Disclaimer: The HPLC images are provided as an information resource only. Bio-Rad Laboratories, Inc and the ITHANET Portal disclaim responsibility and have no liability if this information is used for diagnostic or treatment purposes. D-10™ and VARIANT™ are registered trademarks of Bio-Rad Laboratories, Inc. and used with permission. Redistribution and use of the above material is allowed only with permission by Bio-Rad Laboratories, Inc. To access HPLC images and reports for different variants, use the IthaChrom tool.
ID Hb Variant Gene Instrument Method Area (%) Ret Time (min) Comments
101Hb ProvidenceβD-10Dual Kit Program16.40.97This variant is spontaneously deaminated X-Asn 13-19%; X-Asp 32-33% leading to several fast eluting peaks. [PDF]
606Hb ProvidenceβD-10Dual Kit Program31.30.3This variant is spontaneously deaminated X-Asn 13-19%; X-Asp 32-33% leading to several fast eluting peaks. [PDF]
607Hb ProvidenceβD-10Dual Kit Program16.40.97This variant is spontaneously deaminated X-Asn 13-19%; X-Asp 32-33% leading to several fast eluting peaks. [PDF]

In silico pathogenicity prediction

Publications / Origin

  1. Moo-Penn WF, Jue DL, Bechtel KC, Johnson MH, Schmidt RM, Hemoglobin Providence. A human hemoglobin variant occurring in two forms in vivo., The Journal of biological chemistry, 251(23), 7557-62, 1976
  2. Bonaventura J, Bonaventura C, Sullivan B, Ferruzzi G, McCurdy PR, Fox J, Moo-Penn WF, Hemoglobin providence. Functional consequences of two alterations of the 2,3-diphosphoglycerate binding site at position beta 82., J Biol Chem, 251(23), 7563-71, 1976
  3. Charache S, Fox J, McCurdy P, Kazazian H, Winslow R, Hathaway P, van Beneden R, Jessop M, Postsynthetic deamidation of hemoglobin Providence (beta 82 Lys replaced by Asn, Asp) and its effect on oxygen transport., J Clin Invest, 59(4), 652-8, 1977
  4. Bardakjian J, Leclerc L, Blouquit Y, Oules O, Rafaillat D, Arous N, Bohn B, Poyart C, Rosa J, Galacteros F, A new case of hemoglobin Providence (alpha 2 beta 2 82 (EF6) Lys----Asn or Asp) discovered in a French Caucasian family. Structural and functional studies., Hemoglobin, 9(4), 333-48, 1985
  5. Newman CN, Litwin CM, Bowlby DA, Lewis KA, Paulo RC, Hemoglobin Providence (β82 Lys > Asn, Asp) and lower-than-expected HbA1c in a nonadherent teenager with type 1 diabetes: a case report and literature review., Clin Case Rep, 5(12), 2000-2002, 2017
Created on 2010-06-16 16:13:16, Last reviewed on 2023-06-15 16:46:20 (Show full history)

Disclaimer: The information on this website is provided as an information resource only and must not to be used as a substitute for professional diagnosis and treatment. The ITHANET Portal and IthaGenes are not responsible or liable for any advice, course of treatment, diagnosis or any other information, services or products that an individual obtains through this website.