IthaID: 995

Names and Sequences

Functionality:	Globin gene causative mutation	Pathogenicity:	Variant of Uncertain Significance
Common Name:	CD 58 CCT>CGT [Pro>Arg]	HGVS Name:	HBB:c.176C>G
Hb Name:	Hb Dhofar	Protein Info:	β 58(E2) Pro>Arg

Context nucleotide sequence:
ACTCCTGATGCTGTTATGGGCAACC [C>G] TAAGGTGAAGGCTCATGGCAAGAAA (Strand: -)

Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNRKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Also known as:

Comments: Heterozygotes presented with lower levels of Hb Dhofar (~15%) than expected. Hb Dhofar found in cis with CD 29 GGC>GGT, first in a young man [PMID: 7786794] and then in 54 cases in a cohort study [PMID: 18173741], explaining the lower levels of Dhofar. The CD 29 (C>T) occurs in the consensus splice site boundary of β-globin exon 1, and although it does not alter the amino acid it interferes with the normal mRNA splicing process. All heterozygotes cases presented with elevated Hb A2 and decreased MCV and MCH, consistent with β-thalassaemia trait.

We follow the HGVS sequence variant nomenclature and IUPAC standards.

External Links

HbVar	dbSNP
OMIM	SwissVar

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

IthaPhen

Heterozygous records (preview in IthaPhen)

Location

Chromosome:	11
Locus:	NG_000007.3
Locus Location:	70900
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:	Qara tribesmen in Southern Arabia
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
65	Hb Dhofar	β	D-10	Dual Kit Program	23.5	3.43	Thalassemic Hb (in cis with a beta (+)-thalassemic mutation).	[PDF]
67	Hb Dhofar	β	VARIANT	β-thal Short Program	13.9	3.84	Thalassemic Hb (in cis with a beta (+)-thalassemic mutation).	[PDF]
68	Hb Dhofar	β	VARIANT II	β-thal Short Program	12.8	3.92	Thalassemic Hb (in cis with a beta (+)-thalassemic mutation).	[PDF]
69	Hb Dhofar	β	VARIANT II	Dual Kit Program	18.9	3.12	Thalassemic Hb (in cis with a beta (+)-thalassemic mutation).	[PDF]

In silico pathogenicity prediction

Sequence Viewer

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Frequencies

Publications / Origin

Marengo-Rowe AJ, Lorkin PA, Gallo E, Lehmann H, Haemoglobin Dhofar--a new variant from Southern Arabia., Biochimica et biophysica acta, 168(1), 58-63, 1968 PubMed
Williamson D, Brown KP, Langdown JV, Baglin TP, Haemoglobin Dhofar is linked to the codon 29 C-->T (IVS-1 nt-3) splice mutation which causes beta+ thalassaemia., Br J Haematol, 90(1), 229-31, 1995 PubMed
Daar S, Gravell D, Hussein HM, Pathare AV, Wali Y, Krishnamoorthy R, Haematological and clinical features of beta-thalassaemia associated with Hb Dhofar., Eur J Haematol, 80(1), 67-70, 2008 PubMed

Created on 2010-06-16 16:13:16, Last reviewed on 2022-02-18 00:06:00 (Show full history)

A/A	Date	Curator(s)	Comments
1	2010-06-16 16:13:16	The IthaGenes Curation Team	Created
2	2013-10-15 17:00:14	The IthaGenes Curation Team	Reviewed.
3	2022-02-17 23:40:58	The IthaGenes Curation Team	Reviewed. Comment and References added.
4	2022-02-18 00:06:00	The IthaGenes Curation Team	Reviewed. Protein function added.

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