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NM_000518.5(HBB):c.323dup (p.Asn109fs)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Mar 1, 2020
Accession:
VCV000439153.5
Variation ID:
439153
Description:
1bp duplication
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NM_000518.5(HBB):c.323dup (p.Asn109fs)

Allele ID
432675
Variant type
Duplication
Variant length
1 bp
Cytogenetic location
11p15.4
Genomic location
11: 5225718-5225719 (GRCh38) GRCh38 UCSC
11: 5246948-5246949 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000011.10:g.5225721dup
NC_000011.9:g.5246951dup
NM_000518.5:c.323dup MANE Select NP_000509.1:p.Asn109fs frameshift
... more HGVS
Protein change
N109fs
Other names
CD 106/107 (+G)
Canonical SPDI
NC_000011.10:5225718:CCC:CCCC
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
HBVAR: 945
ClinGen: CA210558
Genetic Testing Registry (GTR): GTR000500319
OMIM: 141900.0329
dbSNP: rs35225141
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Mar 1, 2020 RCV000506185.3
Pathogenic 2 criteria provided, single submitter Jul 3, 2017 RCV000589491.2
Pathogenic 1 criteria provided, single submitter Mar 5, 2019 RCV001002348.1
Pathogenic 1 no assertion criteria provided Nov 26, 1987 RCV000016668.28
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
HBB - - GRCh38
GRCh37
45 1290
LOC107133510 - - - GRCh38 - 1223
LOC110006319 - - - GRCh38 - 573

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jun 30, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601289.1
Submitted: (Aug 01, 2017)
Evidence details
Publications
PubMed (2)
Pathogenic
(Jul 03, 2017)
criteria provided, single submitter
Method: clinical testing
beta Thalassemia
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697119.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (13)
Comment:
Variant summary: The c.323dupG (p.Asn109Glnfs) variant in HBB gene is a frameshift change that is predicted to cause loss of normal protein function through protein … (more)
Pathogenic
(Mar 05, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV001160252.1
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The HBB c.323dupG; p.Asn109fs variant (rs35225141), also known as c.321_322insG and Codon 106/107 (+G), has been reported in individuals with beta thalassemia (Hoppe 2013), and … (more)
Likely pathogenic
(Mar 01, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001384504.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (8)
Comment:
This sequence change results in a premature translational stop signal in the HBB gene (p.Asn109Glnfs*32). While this is not anticipated to result in nonsense mediated … (more)
Pathogenic
(Nov 26, 1987)
no assertion criteria provided
Method: literature only
BETA-ZERO-THALASSEMIA
Allele origin: germline
OMIM
Accession: SCV000036938.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Nov 25, 2019)
no assertion criteria provided
Method: curation
beta Thalassemia
Allele origin: germline
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics
Accession: SCV001244495.1
Submitted: (Nov 25, 2019)
Evidence details
Publications
PubMed (2)
Other databases
https://ithanet.eu/db/ithagenes?…

Functional evidence

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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 this variant

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Title Author Journal Year Link
Rapid detection of pathological mutations and deletions of the haemoglobin beta gene (HBB) by High Resolution Melting (HRM) analysis and Gene Ratio Analysis Copy Enumeration PCR (GRACE-PCR). Turner A BMC medical genetics 2016 PMID: 27756326
Coinheritance of Hb D-Punjab and β-thalassemia: diagnosis and implications in prenatal diagnosis. Das S Hemoglobin 2015 PMID: 25666204
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
Prenatal and newborn screening for hemoglobinopathies. Hoppe CC International journal of laboratory hematology 2013 PMID: 23590658
ThalassoChip, an array mutation and single nucleotide polymorphism detection tool for the diagnosis of β-thalassaemia. Shammas C Clinical chemistry and laboratory medicine 2010 PMID: 20704537
Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes. Sinha S The HUGO journal 2009 PMID: 21119755
Regional heterogeneity of beta-thalassemia mutations in the multi ethnic Indian population. Colah R Blood cells, molecules & diseases 2009 PMID: 19254853
Analysis of beta globin mutations in the Indian population: presence of rare and novel mutations and region-wise heterogeneity. Edison ES Clinical genetics 2008 PMID: 18294253
Rapid detection of beta-globin gene mutations and polymorphisms by temporal temperature gradient gel electrophoresis. Shaji RV Clinical chemistry 2003 PMID: 12709369
Levels of Hb A2 in heterozygotes and homozygotes for beta-thalassemia mutations: influence of mutations in the CACCC and ATAAA motifs of the beta-globin gene promoter. Huisman TH Acta haematologica 1997 PMID: 9401495
Liver iron depletion and toxicity of the iron chelator deferiprone (L1, CP20) in the guinea pig. Wong A Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 1997 PMID: 9353871
Reverse dot-blot detection of the African-American beta-thalassemia mutations. Sutcharitchan P Blood 1995 PMID: 7632967
Molecular characterization of beta-thalassemia in Egyptians. Hussein IR Human mutation 1993 PMID: 8477263
Mean corpuscular volume of heterozygotes for beta-thalassemia correlates with the severity of mutations. Rund D Blood 1992 PMID: 1728311
Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene. Kazazian HH Jr Blood 1992 PMID: 1586746
Molecular characterization of Hb S(C) beta-thalassemia in American blacks. Gonzalez-Redondo JM American journal of hematology 1991 PMID: 1897518
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
Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States. Gonzalez-Redondo JM Blood 1988 PMID: 2458145
Characterization of beta-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA. Wong C Nature 1987 PMID: 3683554
https://ithanet.eu/db/ithagenes?ithaID=231 - - - -

Text-mined citations for rs35225141...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 27, 2021