ClinVar Genomic variation as it relates to human health
NM_000518.4(HBB):c.364G>C (p.Glu122Gln)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000518.4(HBB):c.364G>C (p.Glu122Gln)
Variation ID: 15152 Accession: VCV000015152.124
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.4 11: 5225678 (GRCh38) [ NCBI UCSC ] 11: 5246908 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Apr 20, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000518.5:c.364G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000509.1:p.Glu122Gln missense NC_000011.10:g.5225678C>G NC_000011.9:g.5246908C>G NG_000007.3:g.71938G>C NG_046672.1:g.3613C>G NG_053049.1:g.1999C>G NG_059281.1:g.6394G>C LRG_1232:g.6394G>C LRG_1232t1:c.364G>C LRG_1232p1:p.Glu122Gln P68871:p.Glu122Gln - Protein change
- E122Q
- Other names
- E121Q
- Canonical SPDI
- NC_000011.10:5225677:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00060 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00047
Trans-Omics for Precision Medicine (TOPMed) 0.00017
1000 Genomes Project 0.00060
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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HBB | - | - |
GRCh38 GRCh37 |
21 | 1815 | |
LOC107133510 | - | - | - | GRCh38 | - | 1767 |
LOC110006319 | - | - | - | GRCh38 | - | 976 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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other (1) |
no assertion criteria provided
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Dec 12, 2017 | RCV000016317.17 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Nov 3, 2022 | RCV000029994.19 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 18, 2021 | RCV000202465.15 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000723826.36 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jan 12, 2019 | RCV000778329.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 18, 2019 | RCV001175348.9 | |
Pathogenic (1) |
criteria provided, single submitter
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May 4, 2022 | RCV002247348.9 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jan 27, 2016)
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criteria provided, single submitter
Method: clinical testing
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Beta-thalassemia HBB/LCRB
Affected status: no
Allele origin:
germline
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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Study: CSER-NextGen
Accession: SCV000538040.1 First in ClinVar: Apr 03, 2017 Last updated: Apr 03, 2017 |
Comment:
The c.346G>C (p.Glu534Gln) missense variant, Hb D-Los Angeles, is the fourth most common hemoglobin variant world-wide. Multiple reports identify the variant as pathogenic in combination … (more)
The c.346G>C (p.Glu534Gln) missense variant, Hb D-Los Angeles, is the fourth most common hemoglobin variant world-wide. Multiple reports identify the variant as pathogenic in combination with Hb S. Co-inheritance of Hb D-Los Angeles with Hb S results in Hb SD-Los Angeles (compound heterozygotes) and a moderate to severe clinical phenotype similar to that of sickle cell anemia (SCA). Patients with Hb SD disease have severe hemolytic anemia and recurrent vaso-occlusive episodes. Hb S molecules undergo two-step process leading to nucleation and ultimately the formation of a complex sickle polymer in the deoxygenated state. It is proposed that in the Hb SD-Los Angeles molecule, the Glu122Gln substitution strengthens the second step thereby accelerating polymerization. Thus the Hb D-Los Angeles genotype might increases the probability of sickling (GeneReviews: Origa, 2015, http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1426/, GeneReviews: Bender et al., 2014, http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1377/). This missense variant has significantly increased prevalence in affected individuals relative to controls. Individuals who are either heterozygous or homozygous for the Hb D-Los Angeles variant alone are generally asymptomatic, although rarely, Hb D homozygous individuals can present with mild hemolytic anemia and mild to moderate splenomegaly (GeneReviews: Origa, 2015, http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1426/, GeneReviews: Bender et al., 2014, http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK1377/). Therefore, this collective evidence supports the classification of the c.364G>C (p.Glu122Gln) as a Pathogenic variant for Beta Thalassemia. (less)
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Likely pathogenic
(Jan 12, 2019)
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criteria provided, single submitter
Method: clinical testing
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HBB-Related Disorders
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000914516.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The HBB c.364G>C (p.Glu122Gln) missense variant, which is also reported as p.Glu121Gln, Hb D-Punjab, and Hb D-Los Angeles, is the fourth most common haemoglobin variant … (more)
The HBB c.364G>C (p.Glu122Gln) missense variant, which is also reported as p.Glu121Gln, Hb D-Punjab, and Hb D-Los Angeles, is the fourth most common haemoglobin variant found worldwide. Individuals who carry this variant in a heterozygous or homozygous state are generally asymptomatic, however, inheritance in a homozygous can result in a mild to moderate hemolytic anemia (Taghavi Basmanj et al. 2011; Torres et al. 2015). The p.Glu122Gln variant can occur in association with other hemoglobin variants, for example, HbS or thalassemia, resulting in moderate to severe clinical manifestations resembling a sickle cell disease phenotype or a mild microcytic and hypochromic anemia respectively (Adekile et al. 2010; Bender et al. 2014; Torres et al. 2015). The variant is reported at a frequency of 0.004997 in the South Asian population of the Genome Aggregation Database. Based on the evidence the p.Glu122Gln variant is classified as likely pathogenic for HBB-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Hb SS disease
Affected status: unknown
Allele origin:
germline
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Baylor Genetics
Accession: SCV001163643.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
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Pathogenic
(Mar 01, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449712.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 2
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Pathogenic
(Jul 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001770636.4
First in ClinVar: Aug 07, 2021 Last updated: Mar 04, 2023 |
Comment:
Considered a founder mutation with prevalence in the Punjabi region of India, Italy, Belgium, Austria, and Turkey (Torres Lde et al., 2015); Also referred to … (more)
Considered a founder mutation with prevalence in the Punjabi region of India, Italy, Belgium, Austria, and Turkey (Torres Lde et al., 2015); Also referred to as E121Q due to the use of alternative nomenclature, and commonly called HbD Punjab or HbD Los Angeles (Torres Lde S et al., 2015); Published functional studies suggest a damaging effect, including decreased oxygen affinity of HbD (Narayanan et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 3557998, 25087612, 22975760, 19958184, 25666204, 24123366, 22028795, 2307460, 26680249, 26990548, 8095930, 12403491, 24616059, 2895770, 20110664, 5672850, 4078867, 21194265, 25818823, 24814631, 28970692, 9140717, 30626242, 31553106, 31973650, 31980526, 34426522, 33867742, 6592161, 10490135, 32468185, 1177278) (less)
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Likely pathogenic
(Jan 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601298.3
First in ClinVar: Sep 30, 2017 Last updated: Jan 06, 2024 |
Comment:
In the published literature, individuals who are heterozygous or homozygous for this variant typically have a normal clinical presentation (PMIDs: 30626242 (2018), 25666204 (2015), 24123366 … (more)
In the published literature, individuals who are heterozygous or homozygous for this variant typically have a normal clinical presentation (PMIDs: 30626242 (2018), 25666204 (2015), 24123366 (2014), 12403491 (2002), and 1177278 (1975)). There have been individuals reported to have mild anemia when compound heterozygous with additional HBB variants (PMIDs: 31973650 (2020), 9140717 (1997), and 4078867 (1985)). However, individuals who are compound heterozygous for the Hb D-Los Angeles and Hb S variants have a clinically significant sickling disorder that is similar to sickle cell disease (PMIDs: 25818823 (2015), 24616059 (2014), and 5672850 (1968)). Additionally, individuals who are compound heterozygous for the Hb D-Los Angeles variant and a beta-globin pathogenic variant associated with beta-thalassemia may be affected by beta-thalassemia (PMID: 30626242 (2018), 25087612 (2014), 22028795 (2011), 2307460 (1990)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, this variant is classified as likely pathogenic. (less)
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000957842.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 122 of the HBB protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 122 of the HBB protein (p.Glu122Gln). This variant is present in population databases (rs33946267, gnomAD 0.5%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individuals with an HbSD phenotype, which occurs when this variant is co-inherited with HBB p.Glu7Val (also known as p.Glu6Val and HbS). HbSD is a moderate to severe phenotype similar to that seen in sickle cell anemia. When observed in the heterozygous or homozygous state, this variant is generally asymptomatic. (PMID: 24245819, 24616059, 25666204). This variant is also known as p.Glu121Gln, HbD-Los Angeles, HbD-Punjab, HbD-North-Carolina, HbD-Portugal, and HbD-Chicago. ClinVar contains an entry for this variant (Variation ID: 15152). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HBB protein function. Experimental studies have shown that this missense change affects HBB function (PMID: 2895770). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603898.10
First in ClinVar: Dec 15, 2018 Last updated: Feb 20, 2024 |
Comment:
The Hb D-Los Angeles variant (HBB: c.364G>C; p.Glu122Gln, also known as Glu121Gln when numbered from the mature protein, HbVar ID: 509) is not associated with … (more)
The Hb D-Los Angeles variant (HBB: c.364G>C; p.Glu122Gln, also known as Glu121Gln when numbered from the mature protein, HbVar ID: 509) is not associated with clinical symptoms in heterozygous carriers (HbVar database). Individuals homozygous for Hb D-Los Angeles are also commonly clinically asymptomatic (HbVar database, Torres 2015). Individuals with Hb D-Los Angeles who carry an additional pathogenic variant in their other copy of the beta globin gene may have clinically significant symptoms. Hb D-Los Angeles paired with HbS has a wide phenotypic spectrum ranging from mild to severe sickle cell disease (Perea 1999, Torres 2015 and 2016). Functional studies found an increased rate of nucleation and polymerization in Hb S- D Los Angeles samples as compared with Hb S (Adachi 1988). The clinical presentation in individuals with Hb D-Los Angeles and a beta-thalassemia variant is variable and influenced by the severity of the thalassemia variant, but is commonly characterized by mild to moderate hemolytic anemia (Perea 1999, Theodoridou 2009, Torres 2015 and 2016). This variant is reported in ClinVar (Variation ID: 15152) and is found in the South Asian population with an allele frequency of 0.5% (153/30616 alleles, including 4 homozygotes) in the Genome Aggregation Database. Based on available information, this variant is considered to be pathogenic. REFERENCES Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Adachi K et al. Facilitation of Hb S polymerization by the substitution of Glu for Gln at beta 121. J Biol Chem. 1988 Apr 25;263(12):5607-10. PMID: 2895770. Perea F et al. Hb D-Los Angeles associated with Hb S or beta-thalassemia in four Mexican Mestizo families. Hemoglobin. 1999; 23(3):231-7. PMID: 10490135. Theodoridou S et al. Compound heterozygosity for Hb D-Punjab / beta-thalassemia and blood donation: case report. Turk J Haematol. 2009 Jun 5;26(2):100-1. PMID: 27265282. Torres LS et al. Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis. Rev Bras Hematol Hemoter. 2015 Mar-Apr;37(2):120-6. PMID: 25818823. Torres LS et al. Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab. Hemoglobin. 2016 Sep;40(5):356-358. PMID: 27535451. (less)
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Pathogenic
(Nov 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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beta Thalassemia
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004847541.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Glu122Gln variant in HBB (also known as Glu121Gln, HbD-Los Angeles, HbD-Punjab, HbD-North-Carolina, HbD-Portugal, and HbD-Chicago) is considered a founder mutation in the Punjabi region … (more)
The p.Glu122Gln variant in HBB (also known as Glu121Gln, HbD-Los Angeles, HbD-Punjab, HbD-North-Carolina, HbD-Portugal, and HbD-Chicago) is considered a founder mutation in the Punjabi region of India, Italy, Belgium, Austria, and Turkey (Torres Lde 2015 PMID: 25818823). Heterozygous carriers, but also homozygous individuals, are commonly clinically asymptomatic (HbVar database, Torres Lde 2015 PMID: 25818823). However, individuals who carry this variant in trans with another pathogenic variant may have clinically significant symptoms e.g., sickle cell disease or hemolytic anemia (Perea 1999 PMID: 10490135, Theodoridou 2009 PMID: 27265282, Torres Lde 2015 PMID: 25818823). This variant has also been reported in ClinVar (Variation ID 15152). It has been identified in 21/4828 South Asian and in 10/68032 European chromosomes by gnomAD (https://gnomad.broadinstitute.org/). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In vitro functional studies support an impact on protein function (Adachi 1988 PMID: 2895770). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hemoglobinopathy. ACMG/AMP Criteria applied: PM3_VS, PS3_Moderate. (less)
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Pathogenic
(Feb 11, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000331531.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Pathogenic
(Oct 18, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hemoglobin D disease
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052649.3
First in ClinVar: Apr 04, 2013 Last updated: Jun 22, 2020 |
Comment:
Variant summary: HBB c.364G>C (p.Glu122Gln) results in a conservative amino acid change in the encoded protein sequence and is a common disease-associated variant. The variant … (more)
Variant summary: HBB c.364G>C (p.Glu122Gln) results in a conservative amino acid change in the encoded protein sequence and is a common disease-associated variant. The variant is also cited in the literature as HbD-Los Angeles, HbD-Punjab, HbD-North-Carolina, HbD-Portugal, and HbD-Chicago. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0007 in 251306 control chromosomes in the gnomAD database, including 4 homozygotes. When found in a homozygous or heterozygous state, c.364G>C is typically associated with either no disease phenotype or very mild anemia (e.g. Politis-Tsegos_1975, Rahimi_2006). However, when found in trans with other thalassemia-associated variants, phenotypes can range from mild to severe anemias and splenomegaly (e.g. Worthington_1985, Fucharoen_2002, Rahimi_2006). In addition, patients with this variant in trans with a pathogenic Hgb S variant may have a severe phenotype similar to Sickle Cell Disease (e.g. Mukherjee_2005). These data indicate that the variant is very likely to be associated with disease. At least one study has reported that the p.Glu122Gln protein may facilitate polymerization of Hgb S (Adachi_1998). Seven other laboratories have submitted clinical-significance assessments for this variant to ClinVar (evaluation after 2014), citing the variant four times as pathogenic, two times as likely pathogenic, and one time as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Oct 18, 2019)
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criteria provided, single submitter
Method: clinical testing
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Beta-thalassemia HBB/LCRB
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001193798.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
NM_000518.4(HBB):c.364G>C(E122Q, aka Hb D-Punjab) is classified as likely pathogenic in the context of Hb beta chain-related hemoglobinopathy. Sources cited for classification include the following: PMID … (more)
NM_000518.4(HBB):c.364G>C(E122Q, aka Hb D-Punjab) is classified as likely pathogenic in the context of Hb beta chain-related hemoglobinopathy. Sources cited for classification include the following: PMID 5672850, 3557998, 4078867 and 1177278. Classification of NM_000518.4(HBB):c.364G>C(E122Q, aka Hb D-Punjab) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.‚Äã (less)
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Likely pathogenic
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hb SS disease
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001716384.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Sex: mixed
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Heinz body anemia
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002516535.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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other
(Dec 12, 2017)
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no assertion criteria provided
Method: literature only
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HEMOGLOBIN D (LOS ANGELES)
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000036585.8
First in ClinVar: Apr 04, 2013 Last updated: Mar 25, 2018 |
Comment on evidence:
See Benzer et al. (1958), Bowman and Ingram (1961), Stout et al. (1964), Schneider et al. (1968), Lehmann and Carrell (1969), Ozsoylu (1970), Imamura and … (more)
See Benzer et al. (1958), Bowman and Ingram (1961), Stout et al. (1964), Schneider et al. (1968), Lehmann and Carrell (1969), Ozsoylu (1970), Imamura and Riggs (1972), Bunn et al. (1978), Trent et al. (1984), Worthington and Lehmann (1985), Husquinet et al. (1986), and Harano et al. (1987). Hemoglobin D (Punjab) is common worldwide. It is the most frequent abnormal hemoglobin in Xinjiang Uygur Autonomous Region of China (Li et al., 1986). Zeng et al. (1989) used the PCR method for population studies of this variant. Using PCR and direct sequencing, Schnee et al. (1990) demonstrated the predicted G-to-C substitution in codon 121. (less)
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Pathogenic
(Mar 17, 2017)
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no assertion criteria provided
Method: clinical testing
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Beta thalassemia
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002089185.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Hb SS disease
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000190691.3
First in ClinVar: Dec 21, 2015 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Sickle Cell Disease. | Adam MP | - | 2023 | PMID: 20301551 |
Hb Brugg [HBA1:c.63C>A]: Report of an Ultra-Rare Variant Hemoglobin and Its Co-inheritance with Hb D-Punjab. | Sharma A | Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion | 2021 | PMID: 33867742 |
An Unusual Compound Heterozygosity for Hb O-Arab (HBB: c.364G>A) and Hb D-Los Angeles (HBB: c.364G>C). | van Gammeren AJ | Hemoglobin | 2020 | PMID: 31973650 |
Curating the gnomAD database: Report of novel variants in the globin-coding genes and bioinformatics analysis. | Scheps KG | Human mutation | 2020 | PMID: 31553106 |
Rare Association of Hb D-Los Angeles (HBB: c.364G>C) with Hb H Disease: Diagnosis and Clinical Implications. | Zioga A | Hemoglobin | 2018 | PMID: 30626242 |
Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis. | Torres Lde S | Revista brasileira de hematologia e hemoterapia | 2015 | PMID: 25818823 |
Coinheritance of Hb D-Punjab and β-thalassemia: diagnosis and implications in prenatal diagnosis. | Das S | Hemoglobin | 2015 | PMID: 25666204 |
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results. | Tabor HK | American journal of human genetics | 2014 | PMID: 25087612 |
Haemoglobin sickle d punjab: - a case report. | Rahimah A | The Medical journal of Malaysia | 2014 | PMID: 24814631 |
The effect of hydroxyurea on compound heterozygotes for sickle cell-hemoglobin D-Punjab--a single centre experience in eastern India. | Patel S | Pediatric blood & cancer | 2014 | PMID: 24616059 |
Fetal hemoglobin and alpha thalassemia modulate the phenotypic expression of HbSD-Punjab. | Patel DK | International journal of laboratory hematology | 2014 | PMID: 24245819 |
Exome sequencing identifies potential risk variants for Mendelian disorders at high prevalence in Qatar. | Rodriguez-Flores JL | Human mutation | 2014 | PMID: 24123366 |
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. | Lazarin GA | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22975760 |
In silico analysis of single nucleotide polymorphism (SNPs) in human β-globin gene. | Alanazi M | PloS one | 2011 | PMID: 22028795 |
Co-inheritance of hemoglobin D and β-thalassemia traits in three Iranian families: clinical relevance. | Taghavi Basmanj M | Archives of Iranian medicine | 2011 | PMID: 21194265 |
Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE). | Al-Gazali L | Human mutation | 2010 | PMID: 20437613 |
Does elevated hemoglobin F modulate the phenotype in Hb SD-Los Angeles? | Adekile A | Acta haematologica | 2010 | PMID: 20110664 |
Multi centric origin of Hb D-Punjab [beta121(GH4)Glu-->Gln, GAA>CAA]. | Yavarian M | Hemoglobin | 2009 | PMID: 19958184 |
The beta-globin gene haplotypes associated with Hb D-Los Angeles [beta121(GH4)Glu --> Gln] in Western Iran. | Rahimi Z | Hemoglobin | 2006 | PMID: 16540414 |
High incidence of Hb D-Los Angeles [beta121(GH4)Glu-->Gln] in Denizli Province, Aegean region of Turkey. | Atalay EO | Hemoglobin | 2005 | PMID: 16370495 |
Rapid detection of beta-globin gene mutations and polymorphisms by temporal temperature gradient gel electrophoresis. | Shaji RV | Clinical chemistry | 2003 | PMID: 12709369 |
Molecular characterization of Hb D-Punjab [beta121(GH4)Glu-->Gln] in Thailand. | Fucharoen S | Hemoglobin | 2002 | PMID: 12403491 |
Hb T-Cambodia, a beta chain variant with the mutations of Hb E and Hb D-Punjab, confirmed by DNA analysis. | Hutt PJ | Hemoglobin | 1997 | PMID: 9140717 |
DNA polymorphisms associated with Hb D-Los Angeles [beta 121(GH4)Glu-->Gln] in southern Italy. | Fioretti G | Hemoglobin | 1993 | PMID: 8095930 |
Hb D Los Angeles (D-Punjab) and Hb Presbyterian: analysis of the defect at the DNA level. | Schnee J | Human genetics | 1990 | PMID: 2307460 |
A new slow-moving hemoglobin variant Hb Tianshui or alpha 2 beta(2)39(C5)Gln----Arg, observed in a Chinese family living in Gansu. | Li HJ | Hemoglobin | 1990 | PMID: 2079437 |
Facilitation of Hb S polymerization by the substitution of Glu for Gln at beta 121. | Adachi K | The Journal of biological chemistry | 1988 | PMID: 2895770 |
Hb D Los Angeles [beta 121 Glu----Gln] in Japan. | Harano T | Hemoglobin | 1987 | PMID: 2887538 |
A note about the incidence and origin of Hb D-Punjab in Xinjiang, People's Republic of China. | Li HJ | Hemoglobin | 1986 | PMID: 3557998 |
Hemoglobin D-Los Angeles [beta 121(GH4)Glu----Gln] in the Province of Liège, Belgium. | Husquinet H | Hemoglobin | 1986 | PMID: 3557993 |
The first observation of Hb D Punjab beta zero thalassaemia in an English family with 22 cases of unsuspected beta zero thalassaemia minor among its members. | Worthington S | Journal of medical genetics | 1985 | PMID: 4078867 |
Haemoglobin D Punjab. Interaction with alpha thalassaemia and diagnosis by gene mapping. | Trent RJ | Scandinavian journal of haematology | 1984 | PMID: 6322284 |
Hemoglobin G-Taipei in three additional Chinese families. | Zeng YT | Hemoglobin | 1981 | PMID: 7338475 |
Hemoglobins Aida (alpha 64 Asp leads to Asn) and D-Los Angeles (beta 121 Glu leads to Gln) in an Asian-Indian family. | Bunn HF | Hemoglobin | 1978 | PMID: 750553 |
Globin chain synthesis in HbD (Punjab)-beta-thalassemia. | Rieder RF | Blood | 1976 | PMID: 1244906 |
Homozygous haemoglobin D Punjab. | Politis-Tsegos C | Journal of medical genetics | 1975 | PMID: 1177278 |
Identification of hemoglobin Oak ridge with hemoglobin D Punjab (Los Angeles). | Imamura T | Biochemical genetics | 1972 | PMID: 5050915 |
Homozygous hemoglobin D Punjab. | Ozsoylu S | Acta haematologica | 1970 | PMID: 4991321 |
Hemoglobin D Los Angeles in two Caucasian families: hemoglobin SD disease and hemoglobin D thalassemia. | Schneider RG | Blood | 1968 | PMID: 5672850 |
HEMOGLOBIN D IN AN OKLAHOMA FAMILY. | STOUT C | Archives of internal medicine | 1964 | PMID: 14160125 |
Abnormal human haemoglobins. VII. The comparison of normal human haemoglobin and haemoglobin D-Chicago. | BOWMAN B | Biochimica et biophysica acta | 1961 | PMID: 13872094 |
Three varieties of human haemoglobin D. | LEHMANN H | Nature | 1958 | PMID: 13590135 |
http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=509 | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HBB | - | - | - | - |
http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/sites/GeneTests/review/gene/HBB | - | - | - | - |
Lehmann, H. Haemolyse aufgrund instabiler Haemoglobine. In: Nowicki, L., Martin, H., Schubert, J. C. F. (eds.) Haemolyse-haemolytische Erkrankungen. Munich: J. F. Lehmanns Verlag (pub.) 1973. | - | - | - | - |
Schneider, R. Personal Communication. 1978. Galveston, Tex. | - | - | - | - |
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Text-mined citations for rs33946267 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.