IthaID: 596

Names and Sequences

Functionality:	Globin gene causative mutation	Pathogenicity:	Benign / Likely Benign
Common Name:	CD 68 AAC>AAA [Asn>Lys]	HGVS Name:	HBA2:c.207C>A
Hb Name:	Hb G-Philadelphia	Protein Info:	α2 68(E17) Asn>Lys

Context nucleotide sequence:
AGAAGGTGGCCGACGCGCTGACCAA [C/A] GCCGTGGCGCACGTGGACGACATGC (Strand: +)

Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTKAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR

Also known as: Hb D-Baltimore, Hb D-St. Louis, Hb D-Washington, Hb G-Azakouli, Hb G-Bristol, Hb G-Knoxville, Hb Stanleyville-I

Comments: Reported as a cod68 AAC>AAG change on a chromosome with a normal complement of two α globin genes (αGα/αα) and as a cod68 AAC>AAG change on a chromosome that carries the -α3.7 thalassaemia deletion (-αG/αα) [IthaID: 3973]. Increases in the levels of Hb G-Philadelphia are the result of a deletion of one or more α-globin gene(s): ~25% with four α genes (αGα/αα), ~35% with three α genes (-αG/αα), ~45% with two α genes (-αG/-α), and 100% with one α gene (-αG/--). Different α genotypes present with variable extends of microcytosis and hypochromia, and a decreased ratio of α/β chain synthesis.

We follow the HGVS sequence variant nomenclature and IUPAC standards.

External Links

HbVar	dbSNP
dbSNP	OMIM
SwissVar

Phenotype

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

IthaPhen

Heterozygous records (preview in IthaPhen)

Location

Chromosome:	16
Locus:	NG_000006.1
Locus Location:	34099
Size:	1 bp
Located at:	α2
Specific Location:	Exon 2

Other details

Type of Mutation:	Point-Mutation(Substitution)
Effect on Gene/Protein Function:	Missense codons (Protein Structure)
Ethnic Origin:	African, Chinese, Italian
Molecular mechanism:	N/A
Inheritance:	Recessive
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
351	Hb G-Philadelphia	α2	D-10	Dual Kit Program	22.5	3.96	Heterozygous. Associated with alpha thal.	[PDF]
254	Hb G-Philadelphia	α2	D-10	Dual Kit Program	30	3.92	Heterozygous. Associated with alpha thal.	[PDF]
352	Hb G-Philadelphia	α2	VARIANT	β-thal Short Program	21.7	4.04	Heterozygous. Associated with alpha thal.	[PDF]
255	Hb G-Philadelphia	α2	VARIANT	β-thal Short Program	26.7	4.01	Heterozygous. Eluates as HbD. Associated with alpha thal.	[PDF]
354	Hb G-Philadelphia	α2	VARIANT II	Dual Kit Program	23	3.37	Heterozygous. Elutes as HbS. Associated with alpha thal.	[PDF]
353	Hb G-Philadelphia	α2	VARIANT II	β-thal Short Program	21.5	4.13	Heterozygous. Elutes as HbD. Associated with alpha thal.	[PDF]
257	Hb G-Philadelphia	α2	VARIANT II	Dual Kit Program	28.9	3.35	Heterozygous. Eluates as HbS. Associated with alpha thal.	[PDF]
256	Hb G-Philadelphia	α2	VARIANT II	β-thal Short Program	29	4.12	Heterozygous. Eluates as HbD. Associated with alpha thal.	[PDF]

In silico pathogenicity prediction

Sequence Viewer

Note: The NCBI Sequence Viewer is not installed on the ITHANET servers but it is embedded in this page from the NCBI. Therefore, IthaGenes has no responsibility over any temporary unavailability of the service. In such a case, please Refresh the page or retry at a later stage. Otherwise, use this external link.

Publications / Origin

Bowman BH, Barnett DR, Hodgkinson KT, Schneider RG, Chemical characterization of haemoglobin G-St-I., Nature , 211(5055), 1305-6, 1966 PubMed
Blackwell RQ, Wang CL, Liu CS, Shih TB, Haemoglobin G Philadelphia, alpha68(alphaE17) Asn leads to Lys, in a Chinese subject in Taiwan., Vox Sang. , 25(2), 184-6, 1973 PubMed
Milner PF, Huisman TH, Studies of the proporation and synthesis of haemoblogin C Philadelphia in red cells of heterozygotes, a homozygote, and a heterozygote for both haemoglobin G and alpha thalassaemia., Br. J. Haematol. , 34(2), 207-20, 1976 PubMed
Molchanova TP, Pobedimskaya DD, Huisman TH, The differences in quantities of alpha 2- and alpha 1-globin gene variants in heterozygotes., Br. J. Haematol. , 88(2), 300-6, 1994 PubMed
Molchanova TP, Pobedimskaya DD, Ye Z, Huisman TH, Two different mutations in codon 68 are observed in Hb G-Philadelphia heterozygotes., Am. J. Hematol. , 45(4), 345-6, 1994 PubMed
Khalil MS, Timbs A, Henderson S, Schuh A, Hussein MR, Old J, Haemoglobin (Hb) G-Philadelphia, Hb Stanleyville-II, Hb G-Norfolk, Hb Matsue-Oki and Hb Mizushi can form a panel of α-chain variants that overlap in their phenotype: the novel use of StyI to screen for Hb G-Philadelphia., Int J Lab Hematol, 33(3), 318-25, 2011 PubMed

Created on 2010-06-16 16:13:15, Last reviewed on 2024-03-06 11:02:41 (Show full history)

A/A	Date	Curator(s)	Comments
1	2010-06-16 16:13:15	The IthaGenes Curation Team	Created
2	2013-10-15 17:00:14	The IthaGenes Curation Team	Reviewed.
3	2014-04-10 08:42:10	The IthaGenes Curation Team	Reviewed.
4	2021-04-07 11:27:47	The IthaGenes Curation Team	Reviewed. HGVS, protein name and Locus location corrected. Reference added.
5	2024-03-06 11:02:41	The IthaGenes Curation Team	Reviewed. Comment edited

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.