VCV000011998.93 - ClinVar

NM_000151.4(G6PC1):c.247C>T (p.Arg83Cys)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (27)

27 out of 31 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000151.4(G6PC1):c.247C>T (p.Arg83Cys)

Variation ID: 11998 Accession: VCV000011998.93

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 42903947 (GRCh38) [ NCBI UCSC ] 17: 41055964 (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	Oct 5, 2015	Jun 20, 2026	Jan 24, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_000151.4:c.247C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000142.2:p.Arg83Cys	missense
NM_001270397.2:c.247C>T	NP_001257326.1:p.Arg83Cys	missense
NC_000017.11:g.42903947C>T
NC_000017.10:g.41055964C>T
NG_011808.1:g.8150C>T
LRG_147:g.8150C>T
LRG_147t1:c.247C>T	LRG_147p1:p.Arg83Cys
	NP_000142.1:p.Arg83Cys
	P35575:p.Arg83Cys

... more HGVS ... less HGVS

Protein change

R83C

Other names

G6PC, ARG83CYS

Canonical SPDI

NC_000017.11:42903946:C:T

Global minor allele frequency (GMAF) Help The 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.

The Genome Aggregation Database (gnomAD) 0.00034

Trans-Omics for Precision Medicine (TOPMed) 0.00047

The Genome Aggregation Database (gnomAD), exomes 0.00057

Exome Aggregation Consortium (ExAC) 0.00053

The Genome Aggregation Database (gnomAD) 0.00035

The Genome Aggregation Database (gnomAD), exomes 0.00039

Links

ClinGen: CA256177 Genetic Testing Registry (GTR): GTR000321629 UniProtKB: P35575#VAR_005239 OMIM: 613742.0002 dbSNP: rs1801175 VarSome

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
Gene	OMIM	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.
G6PC1		-	-	GRCh38 GRCh37	630	637

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.
Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Pathogenic (22)	criteria provided, multiple submitters, no conflicts	Jan 24, 2026	RCV000012778.56
Glycogen storage disease	Pathogenic (1)	criteria provided, single submitter	Jun 6, 2016	RCV000360229.7
not provided	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	Nov 28, 2025	RCV000424594.48
Hypoglycemia Short stature	Pathogenic (1)	criteria provided, single submitter	Jan 1, 2017	RCV000626623.3
not specified	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Mar 17, 2024	RCV003987317.5
Glycogen storage disease, type I	Pathogenic (1)	criteria provided, single submitter	Mar 13, 2023	RCV005357111.1

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.	Expand all rows Collapse all rows 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.
Pathogenic (Mar 05, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Genomic Research Center, Shahid Beheshti University of Medical Sciences Accession: SCV000784537.3 First in ClinVar: May 26, 2018 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: inherited Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: inherited Affected status: yes Number of individuals with the variant: 1 Age: 0-9 years Sex: female Geographic origin: Iran

Pathogenic (Nov 28, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000801484.5 First in ClinVar: Aug 04, 2018 Last updated: Jan 11, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 9

Pathogenic (Jan 24, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000658103.10 First in ClinVar: Dec 26, 2017 Last updated: Mar 07, 2026	Publications: PubMed (7) PubMed: 10834516‚ 15316959‚ 18008183‚ 23312056‚ 24385852‚ 7623438‚ 7744838 Comment: show This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 83 of the G6PC protein (p.Arg83Cys). This variant is present in population databases (rs1801175, gnomAD 0.7%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with glycogen storage disease (PMID: 7623438, 10834516, 15316959, 18008183, 23312056, 24385852). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as c.326C>T. ClinVar contains an entry for this variant (Variation ID: 11998). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt G6PC protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects G6PC function (PMID: 7744838). For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Oct 31, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Fulgent Genetics, Fulgent Genetics Accession: SCV000894121.1 First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019	Publications: PubMed (1) PubMed: 25741868 DOI: 10.1038/gim.2015.30 DOI: 10.1038/gim.2015.30 pmc: 4544753 pmc: 4544753 Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Illumina Laboratory Services, Illumina Accession: SCV000402976.3 First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019	Publications: PubMed (11) PubMed: 10612834‚ 10834516‚ 15316959‚ 20301489‚ 21599942‚ 23312056‚ 24385852‚ 7573034‚ 8182131‚ 8211187‚ 9332655 Comment: show The G6PC c.247C>T (p.Arg83Cys) variant is widely reported in the literature as a pathogenic variant for glycogen storage disease type I. The variant has been described in several studies as the most prevalent variant for this disease in the Ashkenazi Jewish population (Ekstein et al. 2004; Bali et al. 2006; Froissart et al. 2011). Across eight studies of individuals of different ethnic origins with glycogen storage disease type I, the p.Arg83Cys variant was reported in 35% (110/312) of alleles including at least 25 individuals in whom the variant was found in a homozygous state and seven in whom the variant was found in a compound heterozygous state (Lei et al. 1993; Lei et al. 1994; Lei et al. 1995; Parvari et al. 1997; Rake et al. 2000; Seydewitz et al. 2000; Sever et al. 2012; Carlin et al. 2013). All individuals showed significantly reduced or undetectable enzyme activity in liver biopsy samples. No control data were available from these studies, though the variant is reported at a frequency of 0.00090 in the European (non-Finnish) population of the Exome Aggregation Consortium. Transient expression studies of the variant by Lei et al. (1993) demonstrated that the p.Arg83Cys abolishes enzyme activity. Based on the collective evidence, the p.Arg83Cys variant is classified as pathogenic for glycogen storage disease type I. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Jun 06, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	Glycogen storage disease (Autosomal recessive inheritance)	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000712202.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Publications: PubMed (2) PubMed: 15316959‚ 8211187 Comment: show The p.Arg83Cys variant in G6PC is the most frequent pathogenic variant implicate d in Glycogen storage disease type I in the Ashkenazi Jewish population (Parvari 1997, Lei 1995, Ekstein 2004). This variant has also been identified 0.09% (60/ 66,646) of European chromosomes by the Exome Aggregation Consortium (ExAC, http: //exac.broadinstitute.org; dbSNP rs1801175). In vitro functional studies also p rovide evidence that the p.Arg83Cys variant may impact protein function (Lei 199 3). In summary, this variant meets our criteria to be classified as pathogenic f or Glycogen storage disease type I in an autosomal recessive manner based upon i ts identification in patients and functional impact. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Number of individuals with the variant: 1

Pathogenic (May 28, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Mendelics Accession: SCV001140451.1 First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Oct 18, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019))	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Myriad Genetics, Inc. Accession: SCV001194060.2 First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020	Publications: PubMed (8) PubMed: 10874313‚ 12093795‚ 12373566‚ 15316959‚ 24082139‚ 7814621‚ 8734807‚ 9332655 Comment: show NM_000151.3(G6PC):c.247C>T(R83C) is classified as pathogenic in the context of glycogen storage disease type Ia. Sources cited for classification include the following: PMID: 10874313, 12093795, 8734807, 7814621, 15316959, 24082139, 12373566, and 9332655. Classification of NM_000151.3(G6PC):c.247C>T(R83C) 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. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Apr 02, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Revvity Omics, Revvity Accession: SCV002023776.4 First in ClinVar: Nov 29, 2021 Last updated: Sep 06, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Nov 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Natera Variant Classification Schema (03/2026))	Glycogen storage disease type Ia	Natera, Inc. Accession: SCV001463398.2 First in ClinVar: Jan 02, 2021 Last updated: Apr 04, 2026	Publications: PubMed (2) PubMed: 12713862‚ 34946936 Comment: show The c.247C>T variant in G6PC1 is a missense variant predicted to cause substitution of arginine to cysteine at amino acid 83. This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 34946936, 12713862). Given the available evidence, this variant is classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Oct 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV001246604.38 First in ClinVar: May 12, 2020 Last updated: Jun 20, 2026	Comment: show G6PC1: PM3:Very Strong, PM1, PM2, PM5, PP4:Moderate, PP3, PS3:Supporting (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 8

Pathogenic (Dec 15, 2014) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease type 1A (Autosomal recessive inheritance)	Knight Diagnostic Laboratories, Oregon Health and Sciences University Accession: SCV000223927.1 First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Pathogenic (May 13, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000695636.1 First in ClinVar: Jan 11, 2018 Last updated: Jan 11, 2018	Publications: PubMed (3) PubMed: 11310582‚ 11739393‚ 25308557 Comment: show Variant summary: The G6PC c.247C>T (p.Arg83Cys) variant involves the alteration of a conserved nucleotide resulting in a replacement of and Arginine with a Cystein located in the conserved phosphatase signature motif of G6PC. Mutations of the phosphatase active site residues are known to be clinically relevant; they predispose individuals to Glycogen Storage Disease (Clinvar, HGMD). Consistently, 5/5 in silico tools predict this variant to be deleterious. The variant was found in 64/121294 control chromosomes (1 homozygote) at a frequency of 0.0005276, which does not exceed the estimated maximal expected allele frequency of a pathogenic G6PC variant (0.0017321). It was reported in several GSD patients in either homozygosity or in compound heterozygosity with other pathogenic variant indicating a disease causing impact. A functional study demonstrated the variant to result in complete inactivation of the enzyme, confirming the importance of an intact Arg83 residue in G6Pase catalysis and further supporting pathogenicity. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as Pathogenic. Taken together, this variant is classified as a Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Jan 01, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hypoglycemia Short stature	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV000747324.1 First in ClinVar: May 12, 2018 Last updated: May 12, 2018	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: yes Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: yes

Pathogenic (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Pathology and Clinical Laboratory Medicine, King Fahad Medical City Accession: SCV000996289.1 First in ClinVar: Oct 19, 2019 Last updated: Oct 19, 2019	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 8 Ethnicity/Population group: Arab Geographic origin: Middle East

Pathogenic (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Baylor Genetics Accession: SCV001163780.1 First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (Autosomal recessive inheritance)	Kids Research, The Children's Hospital at Westmead Accession: SCV001244747.1 First in ClinVar: May 04, 2020 Last updated: May 04, 2020	Publications: PubMed (1) PubMed: 32313153 Observation: 1 Collection method: research Allele origin: inherited Affected status: yes Observation 1 Collection method: research Allele origin: inherited Affected status: yes

Pathogenic (Jan 20, 2022) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000520992.6 First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023	Comment: show Published functional studies demonstrate loss of glucose-6-phosphatase enzyme activity (Shieh et al., 2002; Chou et al., 2008); 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: 12713862, 23312056, 8734807, 25333069, 24082139, 8211187, 18449899, 7623438, 15316959, 11739393, 28360385, 28397058, 29365308, 9664612, 30609409, 30202406, 31980526, 32313153, 33224545, 34426522, 34093448, 34258141, 31589614, 33763395, 33101979, 33258288, 31319225) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (Mar 17, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not specified	Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre Accession: SCV004805179.2 First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024	Observation: 1 Collection method: research Allele origin: germline Affected status: unknown Observation 1 Collection method: research Allele origin: germline Affected status: unknown

Pathogenic (Jun 03, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	not specified	Ambry Genetics Accession: SCV003549547.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Publications: PubMed (10) PubMed: 12713862‚ 28397058‚ 29750741‚ 32313153‚ 33224545‚ 33763395‚ 34093448‚ 7573034‚ 8182131‚ 8211187 Comment: show The c.247C>T (p.R83C) alteration is located in exon 2 (coding exon 2) of the G6PC gene. This alteration results from a C to T substitution at nucleotide position 247, causing the arginine (R) at amino acid position 83 to be replaced by a cysteine (C). Based on data from gnomAD, the T allele has an overall frequency of 0.05% (151/282828) total alleles studied. The highest observed frequency was 0.66% (68/10370) of Ashkenazi Jewish alleles. This alteration has been detected in the homozygous state, and in conjunction with other pathogenic mutations in G6PC1, in multiple individuals with G6PC1-related glycogen storage disease type I (Peeks, 2017; Lei, 1994; Düzenli, 2019; Lei, 1993; Saneifard, 2020; Riley, 2020; Muzetti, 2021; Fang, 2021). It has also been found to segregate in affected individuals in the same family (Carvès, 2003). Another alteration at the same codon, p.R83H (c.248G>A), has been described in individuals with G6PC1-related glycogen storage disease type I (Lei, 1995; Fang, 2021). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Feb 01, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Laboratory of Medical Genetics, National & Kapodistrian University of Athens Accession: SCV005051772.1 First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024	Observation: 1 Collection method: curation Allele origin: germline Affected status: no Observation 1 Collection method: curation Allele origin: germline Affected status: no

Pathogenic (Dec 08, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005088759.2 First in ClinVar: Aug 04, 2024 Last updated: Aug 25, 2024	Comment: show This variant was previously reported in patients with glycogen storage disease in homozygous or compound heterozygous state and reported to segregate with glycogen storage disease type 1a in a family [PMID: 8211187, 23312056, 18008183, 15316959, 15316959, 7623438, 24385852, 10834516]. Functional studies suggested that this variant reduces enzyme activity [PMID: 7744838, 11739393, 18449899]. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (May 15, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV005875332.1 First in ClinVar: Mar 11, 2025 Last updated: Mar 11, 2025	Comment: show The G6PC1 c.247C>T; p.Arg83Cys variant (rs1801175, ClinVar Variation ID: 11998), also known as C326T in the literature, is reported in multiple unrelated individuals with glycogen storage disease who are homozygous or compound heterozygous with another G6PC1 variant (Carves 2003, Chan 2018, Hannah 2022, Lei 1993, Trioche 1998, Qu 1996). This variant is observed in the general population with an overall allele frequency of 0.05% (151/282828 alleles, including 1 homozygote) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is deleterious (REVEL: 0.829). In support of these predictions, functional analyses have shown the variant protein levels are significantly reduced compared to wild type and the variant protein shows abnormal localization (Plona 2021). Based on available information, this variant is considered to be pathogenic. References: Carves C et al. Gouty tendinitis revealing glycogen storage disease Type Ia in two adolescents. Joint Bone Spine. 2003 Mar;70(2):149-53. PMID: 12713862. Chan YM et al. Case 3-2018: A 5-Month-Old Boy with Hypoglycemia. N Engl J Med. 2018 Jan 25;378(4):381-389. PMID: 29365308. Hannah WB et al. Very early-onset inflammatory bowel disease: Novel description in glycogen storage disease type Ia. Mol Genet Metab Rep. 2022 Feb 15;31:100848. PMID: 35242580. Lei KJ et al. Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a. Science. 1993 Oct 22;262(5133):580-3. PMID: 8211187. Plona KL et al. Classifying molecular phenotypes of G6PC variants for pathogenic properties and to guide therapeutic development. JIMD Rep. 2021 Mar 28;60(1):56-66. PMID: 34258141. Trioche P et al. Prenatal diagnosis of glycogen storage disease type Ia by restriction enzyme digestion. Prenat Diagn. 1998 Jun;18(6):629-31. PMID: 9664612. Qu Y et al. Molecular prenatal diagnosis of glycogen storage disease type Ia. Prenat Diagn. 1996 Apr;16(4):333-6. PMID: 8734807. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Jun 27, 2018) C Contributing to aggregate classification	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000227025.6 First in ClinVar: Jun 28, 2015 Last updated: Apr 13, 2025	Publications: PubMed (2) PubMed: 28397058‚ 8211187 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=G6PC Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 13 Zygosity: 1 Homozygote, 12 Single Heterozygotes Sex: mixed

Pathogenic (Mar 13, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	glycogen storage disease I	Department of Pathology and Laboratory Medicine, Sinai Health System Accession: SCV005918132.1 First in ClinVar: Apr 28, 2025 Last updated: Apr 28, 2025	Observation: 1 Collection method: research Allele origin: germline Affected status: unknown Observation 1 Collection method: research Allele origin: germline Affected status: unknown

Pathogenic (Jun 28, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Immunogenetics and Transplant Biology Service, University Hospital "Città della Salute e della Scienza di Torino" Accession: SCV006302916.1 First in ClinVar: Aug 03, 2025 Last updated: Aug 03, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Clinical Features: hypoglycemia (present) , hypotonia (present) , seizures (present)

Pathogenic (Oct 02, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	3billion Accession: SCV002573306.3 First in ClinVar: Sep 17, 2022 Last updated: Jun 20, 2026	Publications: PubMed (2) PubMed: 7655466‚ 8211187 Comment: show The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.040%). Predicted Consequence/Location: Missense variant Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 8211187). In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.83 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.95 (> 0.75, sensitivity 0.96 and precision 0.92)]. The same nucleotide change resulting in the same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000011998 /PMID: 8211187 /3billion dataset). Different missense changes at the same codon (p.Arg83His, p.Arg83Ser) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000038300, VCV002581673 /PMID: 7655466). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Platform type: exome sequencing

Pathogenic (Aug 30, 2004) N Not contributing to aggregate classification	no assertion criteria provided	GLYCOGEN STORAGE DISEASE Ia	OMIM Accession: SCV000033018.3 First in ClinVar: Apr 04, 2013 Last updated: Jan 11, 2018	Publications: PubMed (7) PubMed: 15316959‚ 2172641‚ 7573034‚ 8182131‚ 8211187‚ 8734807‚ 9332655 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: Lei et al. (1993) concluded that a patient with type Ia glycogen storage disease (GSD1A; 232200) was a compound heterozygote for 2 different G6PC mutations: … (more) Lei et al. (1993) concluded that a patient with type Ia glycogen storage disease (GSD1A; 232200) was a compound heterozygote for 2 different G6PC mutations: arg83-to-cys (R83C) and arg295-to-cys (R295C; 613742.0003), located in exons 2 and 5, respectively. The exon 5 mutation came from the father and the exon 2 mutation from the mother. Both mutations were thought to involve a CpG doublet. Lei et al. (1994) demonstrated that the R83C mutant has no detectable phosphohydrolase activity. In a patient originally reported by Burchell and Waddell (1990) as having a novel form of type I glycogen storage disease due to a defect in the 21-kD stabilizing protein SP, Lei et al. (1995) demonstrated that in fact there was an R83C mutation in exon 2 of the G6PC gene. They found the same mutation in both homozygous and heterozygous form in patients with standard GSD type Ia. Qu et al. (1996) performed prenatal diagnosis by chorionic villus sampling in an Ashkenazi Jewish family in which a previous child was homoallelic and both parents were heterozygous for the R83C mutation. Molecular analysis showed that the fetus was not affected. Parvari et al. (1997) found that the R83C mutation was present in all Ashkenazi Jewish patients studied in Israel, suggesting that DNA-based diagnosis may be used as an initial diagnostic step in this population, thus avoiding liver biopsy. Ekstein et al. (2004) tested 20,719 Ashkenazi Jewish subjects for the R83C mutation and identified 290 carriers, giving a carrier frequency of 0.014. The authors noted that this carrier frequency translates into a predicted disease prevalence of 1 in 20,000, 5 times higher than that for the general Caucasian population, confirming a founder effect and elevated frequency of type Ia glycogen storage disease in the Ashkenazi population. They also tested 4,290 Ashkenazi subjects for the Q347X (613742.0004) mutation and found no carriers. Of 30 Ashkenazi Jewish patients with type Ia glycogen storage disease, all were homozygous for the R83C mutation. Ekstein et al. (2004) concluded that R83C is the only prevalent mutation for this disease in the Ashkenazi population. (less)

Pathogenic (Jan 06, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Glycogen storage disease type 1A	Reproductive Health Research and Development, BGI Genomics Accession: SCV001142473.1 First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020	Comment: show NM_000151.3:c.247C>T is also known as c.326C>T in the literature. NM_000151.3:c.247C>T in the G6PC gene has an allele frequency of 0.007 in Ashkenazi Jewish subpopulation in the gnomAD database. This variant has been reported to segregate with glycogen storage disease type 1a in a single family (PMID: 8211187) and has been reported as homozygous or in combination with another G6PC variant in individuals affected with glycogen storage disease type 1A (PMID: 23312056). Ekstein et al reported 30 Glycogen storage disease type Ia patient in Ashkenazi Jewish origin. All of them are homozygous of this variant (PMID: 15316959). Experimental studies have shown that this missense change severely reduces enzyme activity of the protein encoded by G6PC (PMID: 7744838). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PS3; PM3_Strong; PP4; PP1. (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: unknown Observation 1 Collection method: curation Allele origin: germline Affected status: unknown

Likely pathogenic (Oct 11, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City Accession: SCV001469244.1 First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

not provided (-) N Not contributing to aggregate classification	no classification provided	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA	GeneReviews Accession: SCV000040456.3 First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022	Publications: BookShelf: NBK1312 BookShelf: NBK1312 Observation: 1 Collection method: literature only Allele origin: germline Affected status: yes Observation 1 Collection method: literature only Allele origin: germline Affected status: yes

Comment:

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 83 of the G6PC protein (p.Arg83Cys). This variant is present in population databases (rs1801175, gnomAD 0.7%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with glycogen storage disease (PMID: 7623438, 10834516, 15316959, 18008183, 23312056, 24385852). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as c.326C>T. ClinVar contains an entry for this variant (Variation ID: 11998). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt G6PC protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects G6PC function (PMID: 7744838). For these reasons, this variant has been classified as Pathogenic.

Comment:

The G6PC c.247C>T (p.Arg83Cys) variant is widely reported in the literature as a pathogenic variant for glycogen storage disease type I. The variant has been described in several studies as the most prevalent variant for this disease in the Ashkenazi Jewish population (Ekstein et al. 2004; Bali et al. 2006; Froissart et al. 2011). Across eight studies of individuals of different ethnic origins with glycogen storage disease type I, the p.Arg83Cys variant was reported in 35% (110/312) of alleles including at least 25 individuals in whom the variant was found in a homozygous state and seven in whom the variant was found in a compound heterozygous state (Lei et al. 1993; Lei et al. 1994; Lei et al. 1995; Parvari et al. 1997; Rake et al. 2000; Seydewitz et al. 2000; Sever et al. 2012; Carlin et al. 2013). All individuals showed significantly reduced or undetectable enzyme activity in liver biopsy samples. No control data were available from these studies, though the variant is reported at a frequency of 0.00090 in the European (non-Finnish) population of the Exome Aggregation Consortium. Transient expression studies of the variant by Lei et al. (1993) demonstrated that the p.Arg83Cys abolishes enzyme activity. Based on the collective evidence, the p.Arg83Cys variant is classified as pathogenic for glycogen storage disease type I. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

Comment:

The p.Arg83Cys variant in G6PC is the most frequent pathogenic variant implicate d in Glycogen storage disease type I in the Ashkenazi Jewish population (Parvari 1997, Lei 1995, Ekstein 2004). This variant has also been identified 0.09% (60/ 66,646) of European chromosomes by the Exome Aggregation Consortium (ExAC, http: //exac.broadinstitute.org; dbSNP rs1801175). In vitro functional studies also p rovide evidence that the p.Arg83Cys variant may impact protein function (Lei 199 3). In summary, this variant meets our criteria to be classified as pathogenic f or Glycogen storage disease type I in an autosomal recessive manner based upon i ts identification in patients and functional impact.

Comment:

NM_000151.3(G6PC):c.247C>T(R83C) is classified as pathogenic in the context of glycogen storage disease type Ia. Sources cited for classification include the following: PMID: 10874313, 12093795, 8734807, 7814621, 15316959, 24082139, 12373566, and 9332655. Classification of NM_000151.3(G6PC):c.247C>T(R83C) 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.

Comment:

The c.247C>T variant in G6PC1 is a missense variant predicted to cause substitution of arginine to cysteine at amino acid 83. This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 34946936, 12713862). Given the available evidence, this variant is classified as Pathogenic.

Comment:

Variant summary: The G6PC c.247C>T (p.Arg83Cys) variant involves the alteration of a conserved nucleotide resulting in a replacement of and Arginine with a Cystein located in the conserved phosphatase signature motif of G6PC. Mutations of the phosphatase active site residues are known to be clinically relevant; they predispose individuals to Glycogen Storage Disease (Clinvar, HGMD). Consistently, 5/5 in silico tools predict this variant to be deleterious. The variant was found in 64/121294 control chromosomes (1 homozygote) at a frequency of 0.0005276, which does not exceed the estimated maximal expected allele frequency of a pathogenic G6PC variant (0.0017321). It was reported in several GSD patients in either homozygosity or in compound heterozygosity with other pathogenic variant indicating a disease causing impact. A functional study demonstrated the variant to result in complete inactivation of the enzyme, confirming the importance of an intact Arg83 residue in G6Pase catalysis and further supporting pathogenicity. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as Pathogenic. Taken together, this variant is classified as a Pathogenic.

Comment:

Published functional studies demonstrate loss of glucose-6-phosphatase enzyme activity (Shieh et al., 2002; Chou et al., 2008); 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: 12713862, 23312056, 8734807, 25333069, 24082139, 8211187, 18449899, 7623438, 15316959, 11739393, 28360385, 28397058, 29365308, 9664612, 30609409, 30202406, 31980526, 32313153, 33224545, 34426522, 34093448, 34258141, 31589614, 33763395, 33101979, 33258288, 31319225)

Comment:

The c.247C>T (p.R83C) alteration is located in exon 2 (coding exon 2) of the G6PC gene. This alteration results from a C to T substitution at nucleotide position 247, causing the arginine (R) at amino acid position 83 to be replaced by a cysteine (C). Based on data from gnomAD, the T allele has an overall frequency of 0.05% (151/282828) total alleles studied. The highest observed frequency was 0.66% (68/10370) of Ashkenazi Jewish alleles. This alteration has been detected in the homozygous state, and in conjunction with other pathogenic mutations in G6PC1, in multiple individuals with G6PC1-related glycogen storage disease type I (Peeks, 2017; Lei, 1994; Düzenli, 2019; Lei, 1993; Saneifard, 2020; Riley, 2020; Muzetti, 2021; Fang, 2021). It has also been found to segregate in affected individuals in the same family (Carvès, 2003). Another alteration at the same codon, p.R83H (c.248G>A), has been described in individuals with G6PC1-related glycogen storage disease type I (Lei, 1995; Fang, 2021). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

Comment:

This variant was previously reported in patients with glycogen storage disease in homozygous or compound heterozygous state and reported to segregate with glycogen storage disease type 1a in a family [PMID: 8211187, 23312056, 18008183, 15316959, 15316959, 7623438, 24385852, 10834516]. Functional studies suggested that this variant reduces enzyme activity [PMID: 7744838, 11739393, 18449899].

Comment:

The G6PC1 c.247C>T; p.Arg83Cys variant (rs1801175, ClinVar Variation ID: 11998), also known as C326T in the literature, is reported in multiple unrelated individuals with glycogen storage disease who are homozygous or compound heterozygous with another G6PC1 variant (Carves 2003, Chan 2018, Hannah 2022, Lei 1993, Trioche 1998, Qu 1996). This variant is observed in the general population with an overall allele frequency of 0.05% (151/282828 alleles, including 1 homozygote) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is deleterious (REVEL: 0.829). In support of these predictions, functional analyses have shown the variant protein levels are significantly reduced compared to wild type and the variant protein shows abnormal localization (Plona 2021). Based on available information, this variant is considered to be pathogenic. References: Carves C et al. Gouty tendinitis revealing glycogen storage disease Type Ia in two adolescents. Joint Bone Spine. 2003 Mar;70(2):149-53. PMID: 12713862. Chan YM et al. Case 3-2018: A 5-Month-Old Boy with Hypoglycemia. N Engl J Med. 2018 Jan 25;378(4):381-389. PMID: 29365308. Hannah WB et al. Very early-onset inflammatory bowel disease: Novel description in glycogen storage disease type Ia. Mol Genet Metab Rep. 2022 Feb 15;31:100848. PMID: 35242580. Lei KJ et al. Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a. Science. 1993 Oct 22;262(5133):580-3. PMID: 8211187. Plona KL et al. Classifying molecular phenotypes of G6PC variants for pathogenic properties and to guide therapeutic development. JIMD Rep. 2021 Mar 28;60(1):56-66. PMID: 34258141. Trioche P et al. Prenatal diagnosis of glycogen storage disease type Ia by restriction enzyme digestion. Prenat Diagn. 1998 Jun;18(6):629-31. PMID: 9664612. Qu Y et al. Molecular prenatal diagnosis of glycogen storage disease type Ia. Prenat Diagn. 1996 Apr;16(4):333-6. PMID: 8734807.

Comment:

The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.040%). Predicted Consequence/Location: Missense variant Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 8211187). In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.83 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.95 (> 0.75, sensitivity 0.96 and precision 0.92)]. The same nucleotide change resulting in the same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000011998 /PMID: 8211187 /3billion dataset). Different missense changes at the same codon (p.Arg83His, p.Arg83Ser) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000038300, VCV002581673 /PMID: 7655466). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

Comment:

NM_000151.3:c.247C>T is also known as c.326C>T in the literature. NM_000151.3:c.247C>T in the G6PC gene has an allele frequency of 0.007 in Ashkenazi Jewish subpopulation in the gnomAD database. This variant has been reported to segregate with glycogen storage disease type 1a in a single family (PMID: 8211187) and has been reported as homozygous or in combination with another G6PC variant in individuals affected with glycogen storage disease type 1A (PMID: 23312056). Ekstein et al reported 30 Glycogen storage disease type Ia patient in Ashkenazi Jewish origin. All of them are homozygous of this variant (PMID: 15316959). Experimental studies have shown that this missense change severely reduces enzyme activity of the protein encoded by G6PC (PMID: 7744838). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PS3; PM3_Strong; PP4; PP1.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Evaluation of Glycogen Storage Patients: Report of Twelve Novel Variants and New Clinical Findings in a Turkish Population.	Ersoy M	Genes	2021	PMID: 34946936
Neurological Characteristics of Pediatric Glycogen Storage Disease.	Muzetti JH	Frontiers in endocrinology	2021	PMID: 34093448
Clinical and Genetic Spectra of Inherited Liver Disease in Children in China.	Fang Y	Frontiers in pediatrics	2021	PMID: 33763395
Glycogen Storage Disease Type I.	Adam MP	-	2021	PMID: 20301489
A Rare Case of Glycogen Storage Disease Type 1a Presenting with Hemophagocytic Lymphohistiocytosis (HLH).	Saneifard H	Case reports in pediatrics	2020	PMID: 33224545
The diagnostic utility of genome sequencing in a pediatric cohort with suspected mitochondrial disease.	Riley LG	Genetics in medicine : official journal of the American College of Medical Genetics	2020	PMID: 32313153
Hemophagocytic Lymphohystiocytosis Associated With Type Ia Glycogen Storage Disease.	Düzenli Kar Y	Journal of pediatric hematology/oncology	2019	PMID: 29750741
Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control.	Peeks F	Journal of inherited metabolic disease	2017	PMID: 28397058
Regression of hepatocellular adenomas with strict dietary therapy in patients with glycogen storage disease type I.	Beegle RD	JIMD reports	2015	PMID: 25308557
Determining mutations in G6PC and SLC37A4 genes in a sample of Brazilian patients with glycogen storage disease types Ia and Ib.	Carlin MP	Genetics and molecular biology	2013	PMID: 24385852
Personalized genomic disease risk of volunteers.	Gonzalez-Garay ML	Proceedings of the National Academy of Sciences of the United States of America	2013	PMID: 24082139
Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.	Sever S	Journal of clinical lipidology	2012	PMID: 23312056
Glucose-6-phosphatase deficiency.	Froissart R	Orphanet journal of rare diseases	2011	PMID: 21599942
Mutation spectrum of glycogen storage disease type Ia in Tunisia: implication for molecular diagnosis.	Barkaoui E	Journal of inherited metabolic disease	2007	PMID: 18008183
Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population.	Ekstein J	American journal of medical genetics. Part A	2004	PMID: 15316959
Gouty tendinitis revealing glycogen storage disease Type Ia in two adolescents.	Carvès C	Joint bone spine	2003	PMID: 12713862
Glycogen storage disease type I: diagnosis and phenotype/genotype correlation.	Matern D	European journal of pediatrics	2002	PMID: 12373566
The catalytic center of glucose-6-phosphatase. HIS176 is the nucleophile forming the phosphohistidine-enzyme intermediate during catalysis.	Ghosh A	The Journal of biological chemistry	2002	PMID: 12093795
The molecular basis of glycogen storage disease type 1a: structure and function analysis of mutations in glucose-6-phosphatase.	Shieh JJ	The Journal of biological chemistry	2002	PMID: 11739393
Glycogen storage disease type Ia: molecular study in Brazilian patients.	de C Reis F	Journal of human genetics	2001	PMID: 11310582
Identification of mutations in the glucose-6-phosphatase gene in Czech and Slovak patients with glycogen storage disease type ia, including novel mutations K76N, V166A and 540del5.	Kozák L	Human mutation	2000	PMID: 10874313
Glycogen storage disease type Ia: recent experience with mutation analysis, a summary of mutations reported in the literature and a newly developed diagnostic flow chart.	Rake JP	European journal of pediatrics	2000	PMID: 10834516
Molecular genetic analysis of 40 patients with glycogen storage disease type Ia: 100% mutation detection rate and 5 novel mutations.	Seydewitz HH	Human mutation	2000	PMID: 10612834
Glycogen storage disease type 1a in Israel: biochemical, clinical, and mutational studies.	Parvari R	American journal of medical genetics	1997	PMID: 9332655
Molecular prenatal diagnosis of glycogen storage disease type Ia.	Qu Y	Prenatal diagnosis	1996	PMID: 8734807
Mutations in the glucose-6-phosphatase gene are associated with glycogen storage disease types 1a and 1aSP but not 1b and 1c.	Lei KJ	The Journal of clinical investigation	1995	PMID: 7814621
Structure-function analysis of human glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a.	Lei KJ	The Journal of biological chemistry	1995	PMID: 7744838
Glucose-6-phosphatase gene G327A mutation is common in Chinese patients with glycogen storage disease type Ia.	Hwu WL	Human molecular genetics	1995	PMID: 7655466
Characterization of the mutations in the glucose-6-phosphatase gene in Israeli patients with glycogen storage disease type 1a: R83C in six Jews and a novel V166G mutation in a Muslim Arab.	Parvari R	Journal of inherited metabolic disease	1995	PMID: 7623438
Genetic basis of glycogen storage disease type 1a: prevalent mutations at the glucose-6-phosphatase locus.	Lei KJ	American journal of human genetics	1995	PMID: 7573034
Identification of mutations in the gene for glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a.	Lei KJ	The Journal of clinical investigation	1994	PMID: 8182131
Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a.	Lei KJ	Science (New York, N.Y.)	1993	PMID: 8211187
Diagnosis of a novel glycogen storage disease: type 1aSP.	Burchell A	Journal of inherited metabolic disease	1990	PMID: 2172641
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=G6PC	-	-	-	-
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