ClinVar Genomic variation as it relates to human health
NM_000402.4(G6PD):c.961G>A (p.Val321Met)
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_000402.4(G6PD):c.961G>A (p.Val321Met)
Variation ID: 10386 Accession: VCV000010386.93
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154533122 (GRCh38) [ NCBI UCSC ] X: 153761337 (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 Dec 6, 2016 Nov 24, 2024 Oct 9, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001360016.2:c.871G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001346945.1:p.Val291Met missense NM_000402.4:c.961G>A NP_000393.4:p.Val321Met missense NM_001042351.3:c.871G>A NP_001035810.1:p.Val291Met missense NC_000023.11:g.154533122C>T NC_000023.10:g.153761337C>T NG_009015.2:g.19451G>A - Protein change
- V291M, V321M
- Other names
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G6PD, VAL291MET
G6PD Jammu
G6PD Viangchan
- Canonical SPDI
- NC_000023.11:154533121:C:T
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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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0.00159 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00010
Trans-Omics for Precision Medicine (TOPMed) 0.00011
The Genome Aggregation Database (gnomAD), exomes 0.00022
Exome Aggregation Consortium (ExAC) 0.00025
1000 Genomes Project 30x 0.00125
1000 Genomes Project 0.00159
- 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 | ||
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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. |
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G6PD | - | - |
GRCh38 GRCh37 |
- | - |
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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G6PD VIANGCHAN
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other (1) |
no assertion criteria provided
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May 24, 2017 | RCV000011116.12 |
G6PD JAMMU
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other (1) |
no assertion criteria provided
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May 24, 2017 | RCV000011117.12 |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2024 | RCV000405688.14 | |
Pathogenic/Likely pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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Oct 9, 2024 | RCV000180545.39 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jul 1, 2024 | RCV000757320.37 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 20, 2021 | RCV000763203.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 7, 2014 | RCV001266092.10 | |
G6PD deficient hemolytic anemia
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Pathogenic (1) |
criteria provided, single submitter
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- | RCV001250220.9 |
Pathogenic (1) |
criteria provided, single submitter
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Mar 26, 2024 | RCV003460452.2 | |
G6PD-related disorder
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Pathogenic (1) |
no assertion criteria provided
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Jul 14, 2024 | RCV004748513.1 |
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. |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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G6PD deficient hemolytic anemia
Affected status: yes
Allele origin:
germline
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Centogene AG - the Rare Disease Company
Accession: SCV001424422.1
First in ClinVar: Jul 27, 2020 Last updated: Jul 27, 2020 |
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Pathogenic
(Jan 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002580614.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS3, PS4, PM3, PM2_SUP, PP1, PP3
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Number of individuals with the variant: 3
Sex: male
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Pathogenic
(Dec 23, 2021)
|
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: SCV000885495.4
First in ClinVar: Feb 18, 2019 Last updated: Dec 24, 2022 |
Comment:
The G6PD c.871G>A; p.Val291Met variant (rs137852327), also known as G6PD Viangchan, is reported in the literature as a Class II pathogenic variant and is associated … (more)
The G6PD c.871G>A; p.Val291Met variant (rs137852327), also known as G6PD Viangchan, is reported in the literature as a Class II pathogenic variant and is associated with a severe decrease in G6PD enzyme activity (Beutler 1994, Hue 2009, Louicharoen 2005, Matsuoka 2005, Nuchprayoon 2008, Nuchprayoon 2002, Peng 2015, Yusoff 2003). Functional analyses of the variant protein also show reduced enzymatic activity and decreased thermal stability (Boonyuen 2016, Gomez-Manzo 2016). This variant is reported in ClinVar (Variation ID: 10386). This variant is found predominantly in the East Asian population with an allele frequency of 0.25% (35/13,844 alleles, including one homozygote and 13 hemizygotes) in the Genome Aggregation Database. The valine at codon 291 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.94). Based on available information, this variant is considered to be pathogenic. References: Beutler E. G6PD deficiency. Blood. 1994 84:3613-3636. Boonyuen U et al. Detailed functional analysis of two clinical glucose-6-phosphate dehydrogenase (G6PD) variants, G6PDViangchan and G6PDViangchan+Mahidol: Decreased stability and catalytic efficiency contribute to the clinical phenotype. Mol Genet Metab. 2016 118:84-91. Gomez-Manzo S et al. Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan. Int J Mol Sci. 2016 17. Hue NT et al. Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome in the Vietnamese population. Malar J. 2009 8:152. Louicharoen C et al. G6PD Viangchan (871G>A) is the most common G6PD-deficient variant in the Cambodian population. J Hum Genet. 2005 50:448-452. Matsuoka H et al. Glucose-6-phosphate dehydrogenase (G6PD) mutations in Cambodia: G6PD Viangchan (871G>A) is the most common variant in the Cambodian population. J Hum Genet. 2005 50:468-472. Nuchprayoon I et al. Glucose-6-phosphate dehydrogenase mutations in Mon and Burmese of southern Myanmar. J Hum Genet. 2008 53:48-54. Nuchprayoon I et al. Glucose-6-phosphate dehydrogenase (G6PD) mutations in Thailand: G6PD Viangchan (871G>A) is the most common deficiency variant in the Thai population. Hum Mutat. 2002 19:185. Peng Q et al. Large cohort screening of G6PD deficiency and the mutational spectrum in the Dongguan District in Southern China. PLoS One. 2015 10:e0120683. Yusoff NM et al. G6PD Viangchan and G6PD Mediterranean are the main variants in G6PD deficiency in the Malay population of Malaysia. Southeast Asian J Trop Med Public Health. 2003 34 Suppl 3:135-137. (less)
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Pathogenic
(Oct 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Malaria, susceptibility to
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893822.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Pathogenic
(May 31, 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: SCV001874266.3
First in ClinVar: Sep 19, 2021 Last updated: Mar 04, 2023 |
Comment:
Reported to be a common pathogenic variant in Southeast Asian populations (Nuchprayoon et al., 2002); Published functional studies demonstrate that this variant is associated with … (more)
Reported to be a common pathogenic variant in Southeast Asian populations (Nuchprayoon et al., 2002); Published functional studies demonstrate that this variant is associated with lower catalytic constant and catalytic efficiency (Gomez-Manzo et al., 2016); This variant is associated with the following publications: (PMID: 30315739, 26226515, 25775246, 29702993, 30609409, 27053284, 11793482, 29783823, 25536053, 30161219, 3338798, 16136268, 29339739, 11499668, 12850494, 25440321, 23313052, 18329300, 16777444, 1805484, 16155737, 31180159, 34272389, 33072997, 27213370, 31589614, 33083013, 12215013, 27535533) (less)
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Pathogenic
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000951744.7
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 291 of the G6PD protein (p.Val291Met). … (more)
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 291 of the G6PD protein (p.Val291Met). This variant is present in population databases (rs137852327, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individuals with G6PD deficiency (PMID: 15906717, 16155737, 18329300). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 10386). 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) performed at Invitae indicates that this missense variant is expected to disrupt G6PD protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects G6PD function (PMID: 3338798, 27213370). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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Malaria, susceptibility to
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004195381.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Jun 15, 2017)
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criteria provided, single submitter
Method: clinical testing
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000677920.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Pathogenic
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Glucose 6 phosphate dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000482072.3
First in ClinVar: Dec 06, 2016 Last updated: May 27, 2019 |
Comment:
The G6PD c.871G>A (p.Val291Met) variant, also referred to as c.961G>A (p.Val321Met), is well described in the literature as a common variant across several Asian populations … (more)
The G6PD c.871G>A (p.Val291Met) variant, also referred to as c.961G>A (p.Val321Met), is well described in the literature as a common variant across several Asian populations and is often referred to as G6PD Viangchan or G6PD Jammu. The variant was first identified in an individual of Laotian ancestry with glucose-6-phosphate dehydrogenase (G6PD) deficiency (Beutler et al. 1991) and has since been reported as the most common G6PD variant in the Thai and Cambodian populations: Nuchprayoon et al. (2002) identified the p.Val291Met variant in 43 of 76 Thai G6PD deficiency patients, while the variant was reported in a total of 74 of 81 Cambodian G6PD deficiency patients (Matsuoka et al. 2005; Louicharoen et al. 2005). Control data are not reported in these studies for the p.Val291Met variant, which is reported at a frequency of 0.00785 in the East Asian population of the 1000 Genomes Project. Boonyuen et al. (2016) expressed the p.Val291Met variant in E. coli and reported that the KM for glucose-6-phosphate was similar to that of the wild type protein, though the KM for NADP+ was 5-fold higher than wild type and the kcat showed a 10-fold reduction in catalytic efficiency for NADP+ catalysis. Additionally, the variant showed significantly reduced thermostability as compared to wild type. Based on the collective evidence, the p.Val291Met variant is classified as pathogenic for glucose-6-phosphate dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Aug 05, 2015)
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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: SCV000233009.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 14
Sex: mixed
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Likely pathogenic
(Jun 19, 2017)
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criteria provided, single submitter
Method: clinical testing
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
(X-linked inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966815.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
The p.Val321Met (NM_000402.3 c.961G>A) (also referred to as c.871G>A, p.Val291Me t on NM_001042351, G6PD Viangchan and G6PD Jammu) variant in G6PD is one of the … (more)
The p.Val321Met (NM_000402.3 c.961G>A) (also referred to as c.871G>A, p.Val291Me t on NM_001042351, G6PD Viangchan and G6PD Jammu) variant in G6PD is one of the most common variants associated with Glucose-6-phosphate dehydrogenase (G6PD) de ficiency in the Asian population and has been reported in several males (hemizyg ous) and females (heterozygous, compound heterozygous, and homozygous) with G6PD deficiency (Beutler 1991, Peng 2005, Ko 2006, Ninokata 2006, Li 2008, Nuchpray oon 2008, Natakomol 2013, Li 2015). It should be noted that most individuals rep orted with this variant were identified through screening by enzyme testing of a pparently healthy individuals at the time of the study. This variant has been re ported in ClinVar (Variation ID#10386) as a pathogenic variant. It has been ide ntified in 0.24% (33/13881) of East Asian chromosomes including 14 hemizygotes b y the genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; db SNP rs137852327). In vitro functional studies provide evidence that the p.Val321 Met variant may impact protein function (Boonyuen 2016 and Gomez-Manzo 2016). In summary, although additional studies are required to fully establish its clinic al significance, this variant is likely pathogenic for G6PD deficiency in an X-l inked manner based upon its occurrence in individuals with this disorder and da ta from functional studies. (less)
Number of individuals with the variant: 2
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Anemia, nonspherocytic hemolytic, due to G6PD deficiency
(X-linked recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Lifecell International Pvt. Ltd
Accession: SCV001443091.1
First in ClinVar: Nov 14, 2020 Last updated: Nov 14, 2020 |
Comment:
This variant in exon 9 of the G6PD gene results in the amino acid substitution from Valine to Methionine at codon 321 (p.Val321Met) with the … (more)
This variant in exon 9 of the G6PD gene results in the amino acid substitution from Valine to Methionine at codon 321 (p.Val321Met) with the sequence change of c.961G>A (NM_000402.4). This variant was observed in a proband with decreased level of G6PD enzyme (<2.4 U/dL) which was screened for advanced newborn screening with confirmatory genetic reflex testing at Lifecell diagnostics. The variant was first identified with glucose-6-phosphate dehydrogenase ( G6PD) deficiency in a person of Laotian ancestry (Beutler et al . 1991) and has since been recorded as the most common variant of G6PD in the Thai and Cambodian populations. The reference base is conserved across the species and in-silico predictions by Polyphen and SIFT are damaging. The Missense Variants Z-Score for this variant is 2.60. Missense Variants Z-Score is produced by the Exome Aggregation Consortium (60,706 adult humans) by computing a signed Z score for the deviation of observed counts from the expected number. Positive Z scores indicate increased constraint (intolerance to variation) and therefore that the gene had fewer missense variants than expected. The G6PD c.961G>A; p.Val321Met variant, also referred to as c.871G>A; p.Val291Met, commonly known as G6PD Viangchan, has been described in the literature as a Class II to Class III pathogenic variant and is associated with a moderate to severe decrease in enzyme activity (Hue et al., 2009; PMID: 19589177, Nuchprayoon et al., 2002; PMID: 11793482). This variant is one of the most common variants associated with Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Asian population (Beutler et al.,1991; PMID: 1805484, Peng et al., 2005; PMID: 25775246, Ko et al., 2006; PMID: 16777444, Ninokata et al., 2006; PMID: 16528451, Li et al., 2008; PMID: 18329300, Nuchprayoon et al., 2008; PMID: 18046504, Nantakomol et al., 2013; PMID: 23965028, Li et al., 2015; PMID: 26226515). Experimental studies have shown that this missense change impairs G6PD enzyme activity in vitro (Gomez-Manzo et al., 2016; PMID: 27213370 and Boonyuen 2016 et al., PMID: 27053284). (less)
Age: 0-9 years
Sex: male
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Pathogenic
(May 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: unknown
Allele origin:
germline
|
Mendelics
Accession: SCV002516413.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Oct 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV002573775.1
First in ClinVar: Sep 24, 2022 Last updated: Sep 24, 2022 |
Comment:
PM1, PS3, PS4
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|
Pathogenic
(Aug 12, 2022)
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criteria provided, single submitter
Method: curation
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Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: yes
Allele origin:
unknown
|
Dunham Lab, University of Washington
Accession: SCV002599349.1
First in ClinVar: Nov 13, 2022 Last updated: Nov 13, 2022 |
Comment:
Variant found in unrelated hemizygotes with deficiency, some with anemia, favism, and jaundice (PS4_M, PP4). Decreased activity in red blood cells (0-29%) (PS3). Predicted to … (more)
Variant found in unrelated hemizygotes with deficiency, some with anemia, favism, and jaundice (PS4_M, PP4). Decreased activity in red blood cells (0-29%) (PS3). Predicted to be disease causing by Mutation Taster and probably damaging by PolyPhen (PP3). Below expected carrier frequency in gnomAD (PM2). Reported as pathogenic by multiple clinical testing groups (PP5). Post_P 0.997 (odds of pathogenicity 3155, Prior_P 0.1). (less)
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Pathogenic
(Sep 07, 2014)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001444264.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Asian
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Pathogenic
(Jul 20, 2023)
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criteria provided, single submitter
Method: clinical testing
|
Anemia, nonspherocytic hemolytic, due to G6PD deficiency
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002023786.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
|
G6PD deficiency
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004803748.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
Comment:
Variant summary: G6PD c.961G>A (p.Val321Met, also known as G6PD Viangchan) results in a conservative amino acid change located in the Glucose-6-phosphate dehydrogenase, C-terminal (IPR022675) of … (more)
Variant summary: G6PD c.961G>A (p.Val321Met, also known as G6PD Viangchan) results in a conservative amino acid change located in the Glucose-6-phosphate dehydrogenase, C-terminal (IPR022675) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 182854 control chromosomes, predominantly at a frequency of 0.0025 within the East Asian subpopulation in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in G6PD causing Glucose 6 Phosphate Dehydrogenase Deficiency (0.00022 vs 0.29), allowing no conclusion about variant significance. c.961G>A has been reported in the literature in multiple individuals affected with Glucose 6 Phosphate Dehydrogenase Deficiency and has been reported to be a common pathogenic variant in Southeast Asian population (example, Nuchprayoon_2002, Poon_1988). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 40%-50% of catalytic activity of normal G6PD activities in vitro (Boonyuen_2017). The following publications have been ascertained in the context of this evaluation (PMID: 28583873, 11793482, 3338798). ClinVar contains an entry for this variant (Variation ID: 10386). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(May 27, 2022)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005196685.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(Jul 01, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004011706.12
First in ClinVar: Jul 16, 2023 Last updated: Oct 20, 2024 |
Comment:
G6PD: PS3, PS4, PM2
Number of individuals with the variant: 2
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Pathogenic
(Oct 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Anemia, nonspherocytic hemolytic, due to G6PD deficiency
(X-linked recessive inheritance)
Affected status: no
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV003922000.3
First in ClinVar: May 06, 2023 Last updated: Nov 24, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with G6PD deficient hemolytic anemia (favism) (MIM#300908). (I) 0109 - This gene is associated with X-linked recessive disease. Hemizygous males and homozygous females are commonly affected, however some heterozygous female carriers can also be affected depending on X inactivation. (I) 0200 - Variant is predicted to result in a missense amino acid change from valine to methionine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (23 heterozygotes, 1 homozygote, 16 hemizygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant is reported as a common pathogenic variant in the Asian population, also referred to as G6PD Viangchan or G6PD Jammu (ClinVar, PMID: 11793482, 33051526). (SP) 1205 - This variant has been shown to be maternally inherited (by duo analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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other
(May 24, 2017)
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no assertion criteria provided
Method: literature only
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G6PD VIANGCHAN
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000031343.3
First in ClinVar: Apr 04, 2013 Last updated: May 27, 2017 |
Comment on evidence:
See Poon et al. (1988). Beutler (1991) reported a G-to-A mutation at nucleotide 871, resulting in substitution of methionine for valine-291. The variant belonged to … (more)
See Poon et al. (1988). Beutler (1991) reported a G-to-A mutation at nucleotide 871, resulting in substitution of methionine for valine-291. The variant belonged to WHO class 2. Louicharoen and Nuchprayoon (2005) and Matsuoka et al. (2005) indicated that G6PD Viangchan is the most common mutation in the Cambodian population, similar to Thai and Laotian populations, suggesting a common ancestry for people from these 3 countries. Matsuoka et al. (2005) found that G6PD Viangchan was linked in 8 cases with a 1311C-T transition (305900.0018) in exon 11 and a T-to-C substitution in intron 11, 93 bp downstream of exon 11. The finding was in accordance with studies of G6PD Viangchan in Laos, Thailand, and Malaysia. (less)
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other
(May 24, 2017)
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no assertion criteria provided
Method: literature only
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G6PD JAMMU
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000031344.3
First in ClinVar: Apr 04, 2013 Last updated: May 27, 2017 |
Comment on evidence:
See Poon et al. (1988). Beutler (1991) reported a G-to-A mutation at nucleotide 871, resulting in substitution of methionine for valine-291. The variant belonged to … (more)
See Poon et al. (1988). Beutler (1991) reported a G-to-A mutation at nucleotide 871, resulting in substitution of methionine for valine-291. The variant belonged to WHO class 2. Louicharoen and Nuchprayoon (2005) and Matsuoka et al. (2005) indicated that G6PD Viangchan is the most common mutation in the Cambodian population, similar to Thai and Laotian populations, suggesting a common ancestry for people from these 3 countries. Matsuoka et al. (2005) found that G6PD Viangchan was linked in 8 cases with a 1311C-T transition (305900.0018) in exon 11 and a T-to-C substitution in intron 11, 93 bp downstream of exon 11. The finding was in accordance with studies of G6PD Viangchan in Laos, Thailand, and Malaysia. (less)
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Pathogenic
(Jul 14, 2024)
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no assertion criteria provided
Method: clinical testing
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G6PD-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005364206.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The G6PD c.871G>A variant is predicted to result in the amino acid substitution p.Val291Met. This variant, also referred to as G6PD Viangchan/Jammu, has previously been … (more)
The G6PD c.871G>A variant is predicted to result in the amino acid substitution p.Val291Met. This variant, also referred to as G6PD Viangchan/Jammu, has previously been reported to be causative for Glucose-6-Phosphate Dehydrogenase Deficiency. This variant is probably the most common causative variant in non-Chinese Southeast Asian population (Nuchprayoon et al. 2008. PubMed ID: 18046504; Boonyuen et al. 2016. PubMed ID: 27053284). This variant is reported in 0.25% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as pathogenic. (less)
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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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Cut-off values for diagnosis of G6PD deficiency by flow cytometry in Thai population. | Thedsawad A | Annals of hematology | 2022 | PMID: 35840819 |
Molecular characterization of G6PD mutations reveals the high frequency of G6PD Aures in the Lao Theung population. | Sanephonasa A | Malaria journal | 2021 | PMID: 33413378 |
Glucose-6-phosphate dehydrogenase deficiency in the Han Chinese population: molecular characterization and genotype-phenotype association throughout an activity distribution. | He Y | Scientific reports | 2020 | PMID: 33051526 |
Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation. | Alina MF | Journal of human genetics | 2020 | PMID: 31863082 |
Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017. | Liu Z | Human mutation | 2020 | PMID: 31489982 |
Incidence of Glucose-6-Phosphate Dehydrogenase Deficiency among Swedish Newborn Infants. | Ohlsson A | International journal of neonatal screening | 2019 | PMID: 33072997 |
G6PD genetic variations in neonatal Hyperbilirubinemia in Indonesian Deutromalay population. | Wisnumurti DA | BMC pediatrics | 2019 | PMID: 31862010 |
Genotype-Phenotype Correlations of Glucose-6-Phosphate-Deficient Variants Throughout an Activity Distribution. | Powers JL | The journal of applied laboratory medicine | 2018 | PMID: 33636823 |
Mutation of glucose-6-phosphate dehydrogenase deficiency in Chinese Han children in eastern Fujian. | Chen Y | Medicine | 2018 | PMID: 30045279 |
Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates. | Fu C | Scientific reports | 2018 | PMID: 29339739 |
A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency. | Boonyuen U | International journal of biological macromolecules | 2017 | PMID: 28583873 |
Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan. | Gómez-Manzo S | International journal of molecular sciences | 2016 | PMID: 27213370 |
Detailed functional analysis of two clinical glucose-6-phosphate dehydrogenase (G6PD) variants, G6PDViangchan and G6PDViangchan+Mahidol: Decreased stability and catalytic efficiency contribute to the clinical phenotype. | Boonyuen U | Molecular genetics and metabolism | 2016 | PMID: 27053284 |
Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border. | Li Q | PloS one | 2015 | PMID: 26226515 |
Large cohort screening of G6PD deficiency and the mutational spectrum in the Dongguan District in Southern China. | Peng Q | PloS one | 2015 | PMID: 25775246 |
Field trial evaluation of the performances of point-of-care tests for screening G6PD deficiency in Cambodia. | Roca-Feltrer A | PloS one | 2014 | PMID: 25541721 |
Characterization of G6PD genotypes and phenotypes on the northwestern Thailand-Myanmar border. | Bancone G | PloS one | 2014 | PMID: 25536053 |
Evaluation of the phenotypic test and genetic analysis in the detection of glucose-6-phosphate dehydrogenase deficiency. | Nantakomol D | Malaria journal | 2013 | PMID: 23965028 |
Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating with disease severity. | Dallol A | Journal of translational medicine | 2012 | PMID: 23006493 |
Performance of the CareStart™ G6PD deficiency screening test, a point-of-care diagnostic for primaquine therapy screening. | Kim S | PloS one | 2011 | PMID: 22164279 |
Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome in the Vietnamese population. | Hue NT | Malaria journal | 2009 | PMID: 19589177 |
Development and evaluation of a reverse dot blot assay for the simultaneous detection of six common Chinese G6PD mutations and one polymorphism. | Li L | Blood cells, molecules & diseases | 2008 | PMID: 18329300 |
Glucose-6-phosphate dehydrogenase mutations in Mon and Burmese of southern Myanmar. | Nuchprayoon I | Journal of human genetics | 2008 | PMID: 18046504 |
Multiplex primer extension reaction screening and oxidative challenge of glucose-6-phosphate dehydrogenase mutants in hemizygous and heterozygous subjects. | Ko CH | Blood cells, molecules & diseases | 2006 | PMID: 16777444 |
Coexistence of five G6PD variants indicates ethnic complexity of Phuket islanders, Southern Thailand. | Ninokata A | Journal of human genetics | 2006 | PMID: 16528451 |
Glucose-6-phosphate dehydrogenase variants associated with favism in Thai children. | Laosombat V | International journal of hematology | 2006 | PMID: 16513531 |
G6PD Viangchan (871G>A) is the most common G6PD-deficient variant in the Cambodian population. | Louicharoen C | Journal of human genetics | 2005 | PMID: 16155737 |
Glucose-6-phosphate dehydrogenase (G6PD) mutations in Cambodia: G6PD Viangchan (871G>A) is the most common variant in the Cambodian population. | Matsuoka H | Journal of human genetics | 2005 | PMID: 16136268 |
Molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) variants in the south of Thailand and identification of a novel variant (G6PD Songklanagarind). | Laosombat V | Blood cells, molecules & diseases | 2005 | PMID: 15727905 |
Complete molecular characterisation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a group of Malaysian Chinese neonates. | Ainoon O | The Malaysian journal of pathology | 2004 | PMID: 16329560 |
G6PD Viangchan and G6PD Mediterranean are the main variants in G6PD deficiency in the Malay population of Malaysia. | Yusoff NM | The Southeast Asian journal of tropical medicine and public health | 2003 | PMID: 15906717 |
Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Malays. | Ainoon O | Human mutation | 2003 | PMID: 12497642 |
Glucose-6-phosphate dehydrogenase (G6PD) mutations in Thailand: G6PD Viangchan (871G>A) is the most common deficiency variant in the Thai population. | Nuchprayoon I | Human mutation | 2002 | PMID: 11793482 |
Glucose-6 phosphate dehydrogenase mutations and haplotypes in various ethnic groups. | Xu W | Blood | 1995 | PMID: 7803800 |
Frequency of glucose-6-phosphate dehydrogenase (G6PD) mutations in Chinese, Filipinos, and Laotians from Hawaii. | Hsia YE | Human genetics | 1993 | PMID: 8244337 |
Glucose-6-phosphate dehydrogenase variants in Hawaii. | Beutler E | Human heredity | 1992 | PMID: 1459579 |
Definition of the mutations of G6PD Wayne, G6PD Viangchan, G6PD Jammu, and G6PD 'LeJeune'. | Beutler E | Acta haematologica | 1991 | PMID: 1805484 |
Glucose-6-phosphate dehydrogenase deficiency. WHO Working Group. | - | Bulletin of the World Health Organization | 1989 | PMID: 2633878 |
G6PD Viangchan: a new glucose 6-phosphate dehydrogenase variant from Laos. | Poon MC | Human genetics | 1988 | PMID: 3338798 |
Beutler, E., Keller, J. W., Matsumoto, F. A new glucose 6-phosphate dehydrogenase (G6PD) variant associated with nonspherocytic hemolytic anemia: G6PD Atlanta. I.R.C.S. 4: 479, 1976. | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=G6PD | - | - | - | - |
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Text-mined citations for rs137852327 ...
HelpRecord 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.