Reported in multiple individuals with mild anemia or normal clinical and hematological parameters (Schneider et al., 1976; Basak et al., 2014; Kutlar et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24471829, 11829, 31553106, 24802353, 19429541, 33054450)
ClinVar Genomic variation as it relates to human health
NM_000518.5(HBB):c.359G>A (p.Gly120Asp)
Germline
Classification
Help
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.
(5)
Help
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.
Conflicting classifications of pathogenicity
Uncertain significance(4); Likely benign(1)
Uncertain significance(4); Likely benign(1)
5
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
This variant is part of 2 Haplotypes
- Identifiers
-
NM_000518.5(HBB):c.359G>A (p.Gly120Asp)
Variation ID: 242712 Accession: VCV000242712.19
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.4 11: 5225683 (GRCh38) [ NCBI UCSC ] 11: 5246913 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Mar 17, 2018 Jul 15, 2024 Apr 2, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000518.5:c.359G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000509.1:p.Gly120Asp missense NC_000011.10:g.5225683C>T NC_000011.9:g.5246913C>T NG_000007.3:g.71933G>A NG_046672.1:g.3618C>T NG_053049.1:g.2004C>T NG_059281.1:g.6389G>A LRG_1232:g.6389G>A LRG_1232t1:c.359G>A LRG_1232p1:p.Gly120Asp - Protein change
- G120D
- Other names
-
G119D
- Canonical SPDI
- NC_000011.10:5225682:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00002
- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| HBB | - | - |
GRCh38 GRCh37 |
22 | 1835 | |
| LOC107133510 | - | - | - | GRCh38 | - | 1785 |
| LOC110006319 | - | - | - | GRCh38 | - | 984 |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Oct 17, 2023 | RCV000588047.28 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 2, 2024 | RCV004586649.1 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Mar 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002013797.2
First in ClinVar: Nov 13, 2021 Last updated: Mar 04, 2023 |
Comment:
Reported in multiple individuals with mild anemia or normal clinical and hematological parameters (Schneider et al., 1976; Basak et al., 2014; Kutlar et al., 2014); … (more)
Reported in multiple individuals with mild anemia or normal clinical and hematological parameters (Schneider et al., 1976; Basak et al., 2014; Kutlar et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24471829, 11829, 31553106, 24802353, 19429541, 33054450) (less)
|
|
|
Uncertain significance
(Mar 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888157.6
First in ClinVar: Feb 17, 2019 Last updated: Jan 06, 2024 |
Comment:
The HBB c.359G>A (p.Gly120Asp) variant (also known as Hb Fannin-Lubbock I) has been reported in the published literature as a slightly unstable hemoglobin variant, with … (more)
The HBB c.359G>A (p.Gly120Asp) variant (also known as Hb Fannin-Lubbock I) has been reported in the published literature as a slightly unstable hemoglobin variant, with normal oxygen affinity (PMIDs: 19958195 (2009), 7852084 (1994), 11829 (1976)). Heterozygosity for the Hb Fannin-Lubbock I variant is associated with a normal clinical presentation (PMID: 24802353 (2014), 11829 (1976)). The frequency of this variant in the general population, 0.00017 (6/34586 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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, we are unable to determine the clinical significance of this variant. (less)
|
|
|
Uncertain significance
(Jun 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV004235259.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
|
|
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Likely benign
(Oct 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603903.7
First in ClinVar: Sep 30, 2017 Last updated: Feb 20, 2024 |
|
|
|
Uncertain significance
(Apr 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697124.2
First in ClinVar: Mar 17, 2018 Last updated: Jul 15, 2024 |
Comment:
Variant summary: HBB c.359G>A (p.Gly120Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging … (more)
Variant summary: HBB c.359G>A (p.Gly120Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251278 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. This variant has been reported in multiple patients with mild anemia or no hemological abnormalities in heterozygous or homozygous state without clear evidence supporting the pathogenicity of this variant (Schneider_1976, Ibarra_2009, Basak_2014). Heterozygous complex allele c.334G>C-c.359G>A has been reported in five Spanish individuals with no hemological abnormalities (Qin_1994). Experimental evidence has shown this variant to be a slightly unstable hemoglobin variant, with normal oxygen affinity (eg. Schneider_1976). The following publications have been ascertained in the context of this evaluation (PMID: 6859036, 19429541, 7852084, 24802353, 19958195, 11829, 20184100). ClinVar contains an entry for this variant (Variation ID: 242712). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
Comment:
Comment:
The HBB c.359G>A (p.Gly120Asp) variant (also known as Hb Fannin-Lubbock I) has been reported in the published literature as a slightly unstable hemoglobin variant, with normal oxygen affinity (PMIDs: 19958195 (2009), 7852084 (1994), 11829 (1976)). Heterozygosity for the Hb Fannin-Lubbock I variant is associated with a normal clinical presentation (PMID: 24802353 (2014), 11829 (1976)). The frequency of this variant in the general population, 0.00017 (6/34586 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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, we are unable to determine the clinical significance of this variant.
Comment:
Variant summary: HBB c.359G>A (p.Gly120Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251278 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. This variant has been reported in multiple patients with mild anemia or no hemological abnormalities in heterozygous or homozygous state without clear evidence supporting the pathogenicity of this variant (Schneider_1976, Ibarra_2009, Basak_2014). Heterozygous complex allele c.334G>C-c.359G>A has been reported in five Spanish individuals with no hemological abnormalities (Qin_1994). Experimental evidence has shown this variant to be a slightly unstable hemoglobin variant, with normal oxygen affinity (eg. Schneider_1976). The following publications have been ascertained in the context of this evaluation (PMID: 6859036, 19429541, 7852084, 24802353, 19958195, 11829, 20184100). ClinVar contains an entry for this variant (Variation ID: 242712). Based on the evidence outlined above, the variant was classified as uncertain significance.
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. |
Comment:
Reported in multiple individuals with mild anemia or normal clinical and hematological parameters (Schneider et al., 1976; Basak et al., 2014; Kutlar et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24471829, 11829, 31553106, 24802353, 19429541, 33054450)
Comment:
The HBB c.359G>A (p.Gly120Asp) variant (also known as Hb Fannin-Lubbock I) has been reported in the published literature as a slightly unstable hemoglobin variant, with normal oxygen affinity (PMIDs: 19958195 (2009), 7852084 (1994), 11829 (1976)). Heterozygosity for the Hb Fannin-Lubbock I variant is associated with a normal clinical presentation (PMID: 24802353 (2014), 11829 (1976)). The frequency of this variant in the general population, 0.00017 (6/34586 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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, we are unable to determine the clinical significance of this variant.
Comment:
Variant summary: HBB c.359G>A (p.Gly120Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251278 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. This variant has been reported in multiple patients with mild anemia or no hemological abnormalities in heterozygous or homozygous state without clear evidence supporting the pathogenicity of this variant (Schneider_1976, Ibarra_2009, Basak_2014). Heterozygous complex allele c.334G>C-c.359G>A has been reported in five Spanish individuals with no hemological abnormalities (Qin_1994). Experimental evidence has shown this variant to be a slightly unstable hemoglobin variant, with normal oxygen affinity (eg. Schneider_1976). The following publications have been ascertained in the context of this evaluation (PMID: 6859036, 19429541, 7852084, 24802353, 19958195, 11829, 20184100). ClinVar contains an entry for this variant (Variation ID: 242712). Based on the evidence outlined above, the variant was classified as uncertain significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Analysis of a Novel Mexican Variant of the HBB Gene Associated with β-Thalassemia Using Bioinformatic Tools. | Martínez Villegas O | Hemoglobin | 2021 | PMID: 34060411 |
| Curating the gnomAD database: Report of novel variants in the globin-coding genes and bioinformatics analysis. | Scheps KG | Human mutation | 2020 | PMID: 31553106 |
| Hb Belluno [β111(G13)Val→Gly;β133(H11)Val→Val (HBB: c.335T > G;402G > C)]: Incidental Detection of a New Clinically Silent β Chain Variant During Hb A1c Determination by High Performance Liquid Chromatography. | Pianezze G | Hemoglobin | 2016 | PMID: 27032675 |
| Fannin-Lubbock-I [α₂β₂¹¹⁹(GLY>ASP)], a rare mutation in the beta-globin gene, has been detected for the first time in a Hindu Brahmin family in West Bengal, India. | Basak J | Cellular & molecular biology letters | 2014 | PMID: 24802353 |
| Two new hemoglobin variants: Hb Tallahassee [α3(A1)Ser→Tyr; HBA2: c.11C>A] and Hb madison-NC [β119(GH2)Gly→Ser; HBB: c.358G>A]. | Kutlar F | Hemoglobin | 2014 | PMID: 24471829 |
| Types and frequencies of hemoglobin disorders in the pacific coast of four states of Mexico. | Cobián JG | Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion | 2009 | PMID: 20184100 |
| HB Fannin-Lubbock-I with a single GGC>GAC mutation at beta119(GH2)Gly-->Asp in a homozygous Mexican patient. | Ibarra B | Hemoglobin | 2009 | PMID: 19958195 |
| Impact of single nucleotide polymorphisms in HBB gene causing haemoglobinopathies: in silico analysis. | George Priya Doss C | New biotechnology | 2009 | PMID: 19429541 |
| Hb Fannin-Lubbock in five Spanish families is characterized by two mutations: beta 111 GTC-->CTC (Val-->Leu) and beta 119 GGC-->GAC (Gly-->Asp). | Qin WB | Hemoglobin | 1994 | PMID: 7852084 |
| Percentages of abnormal hemoglobins in adults with a heterozygosity for an alpha-chain and/or a beta-chain variant. | Huisman TH | American journal of hematology | 1983 | PMID: 6859036 |
| Hemoglobin Fannin-Lubbock [alpha 2 beta 2 119(GH2) Gly replaced by Asp]. A slightly unstable mutant. | Schneider RG | Biochimica et biophysica acta | 1976 | PMID: 11829 |
| Hemoglobin Fannin-Lubbock [alpha2 beta 2 119 (GH2) Gly replaced by Asp]. A new hemoglobin variant at the alpha1 beta 1 contact. | Moo-Penn WF | Biochimica et biophysica acta | 1976 | PMID: 11828 |
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Text-mined citations for rs33947020 ...
HelpThese 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 Nov 25, 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.