ClinVar Genomic variation as it relates to human health
NM_000151.4(G6PC1):c.79del (p.Gln27fs)
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_000151.4(G6PC1):c.79del (p.Gln27fs)
Variation ID: 21062 Accession: VCV000021062.37
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 42900953 (GRCh38) [ NCBI UCSC ] 17: 41052970 (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 Aug 29, 2016 Apr 15, 2024 Jan 22, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000151.4:c.79del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000142.2:p.Gln27fs frameshift NM_000151.2:c.79delC NM_000151.3:c.79del NM_001270397.2:c.79del NP_001257326.1:p.Gln27fs frameshift NC_000017.11:g.42900955del NC_000017.10:g.41052972del NG_011808.1:g.5158del LRG_147:g.5158del LRG_147t1:c.79del LRG_147p1:p.Gln27ArgfsTer9 - Protein change
- Q27fs
- Other names
- 158delC
- Canonical SPDI
- NC_000017.11:42900952:CCC:CC
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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G6PC1 | - | - |
GRCh38 GRCh37 |
560 | 566 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Jan 4, 2024 | RCV000173073.22 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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May 1, 2023 | RCV000199426.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 25, 2020 | RCV001449697.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 22, 2024 | RCV003421926.5 |
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
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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
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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
(Oct 01, 2014)
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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: SCV000224157.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Pathogenic
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000402975.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The G6PC c.79delC (p.Gln27ArgfsTer9) variant results in a frameshift and is predicted to result in premature termination of the protein. The variant is also described … (more)
The G6PC c.79delC (p.Gln27ArgfsTer9) variant results in a frameshift and is predicted to result in premature termination of the protein. The variant is also described in the literature as c.77delC or 158delC. Koeberl et al. (2009) describe the p.Gln27ArgfsTer9 variant as a common variant occurring in up to 5% of Caucasian individuals with glycogen storage disease type 1a. The p.Gln27ArgfsTer9 variant has been reported in five studies in which it is found in a total of 14 individuals including in seven in a homozygous state and seven in a compound heterozygous state (Chevalier-Porst et al. 1996; Rake et al. 1999; Shieh et al. 2002; Angaroni et al. 2004; Kishnani et al. 2009). The variant was additionally found in 7/192 disease alleles in two studies where zygosity data were not available (Lei et al. 1995; Seydewitz et al. 2000). Control data are unavailable for this variant which is reported at a frequency of 0.00235 in the African American population of the Exome Sequencing Project. Several studies report very low or undetectable enzyme activity in liver biopsy specimens indicating the inactivation of the enzyme by the p.Gln27ArgfsTer9 variant (Lei et al. 1995; Chevalier-Porst et al. 1996; Seydewitz et al. 2000; Rake et al. 1999). Chevalier-Porst et al. (1996) also described elevated glycogen content in the liver in an individual who was homozygous for the p.Gln27ArgfsTer9 variant. Based on the collective evidence, the p.Gln27ArgfsTer9 variant is classified as pathogenic for glycogen storage disease type 1. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: unknown
Allele origin:
germline
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Baylor Genetics
Accession: SCV001163776.1
First in ClinVar: Feb 28, 2020 Last updated: Feb 28, 2020 |
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Pathogenic
(Nov 15, 2019)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001194026.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 03, 2020 |
Comment:
NM_000151.3(G6PC):c.79delC(Q27Rfs*9) is classified as pathogenic in the context of type Ia glycogen storage disease. Sources cited for classification include the following: PMID 10834516, 12373566, 10874313, … (more)
NM_000151.3(G6PC):c.79delC(Q27Rfs*9) is classified as pathogenic in the context of type Ia glycogen storage disease. Sources cited for classification include the following: PMID 10834516, 12373566, 10874313, 20532819, 23352793, 7573034, 17994282 and 11949931. Classification of NM_000151.3(G6PC):c.79delC(Q27Rfs*9) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Jun 25, 2020)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type I
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV001652950.1
First in ClinVar: May 29, 2021 Last updated: May 29, 2021 |
Comment:
The p.Gln27ArgfsX9 variant in G6PC has been reported in at least 4 homozgyous and 2 compound heterozygous individuals with Glycogen storage disease, and reported without … (more)
The p.Gln27ArgfsX9 variant in G6PC has been reported in at least 4 homozgyous and 2 compound heterozygous individuals with Glycogen storage disease, and reported without allele state information in an additional 6 individuals with Glycogen storage disease (Lei 1995 PMID: 7573034, Chevalier-Porst 1996 PMID: 8733042, Rake 1999 PMID: 10094563, Angaroni 2004 PMID: 15542400). It has also been identified in 0.011% (14/129190) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). However, this frequency is low enough to be consistent with a recessive allele frequency. This variant is reported in ClinVar (Variation ID: 21062). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 27 and leads to a premature termination codon 9 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the G6PC gene is an established disease mechanism in autosomal recessive Glycogen storage disease. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Glycogen storage disease. ACMG/AMP Criteria applied: PVS1, PM3_Strong, PM2_Supporting. (less)
Number of individuals with the variant: 1
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Pathogenic
(Jan 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003820043.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000947971.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln27Argfs*9) in the G6PC gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln27Argfs*9) in the G6PC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in G6PC are known to be pathogenic (PMID: 8182131). This variant is present in population databases (rs768209865, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with glycogen storage disease (PMID: 10094563, 11739393, 16435186, 28397058). This variant is also known as 158delC. ClinVar contains an entry for this variant (Variation ID: 21062). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 22, 2024)
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criteria provided, single submitter
Method: clinical testing
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G6PC1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004118363.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
The G6PC1 c.79delC variant is predicted to result in a frameshift and premature protein termination (p.Gln27Argfs*9). This variant has previously been reported in the homozygous … (more)
The G6PC1 c.79delC variant is predicted to result in a frameshift and premature protein termination (p.Gln27Argfs*9). This variant has previously been reported in the homozygous and compound heterozygous state in multiple patients with glycogen storage disease type Ia (GSD Ia) (e.g., Lei et al. 1995. PubMed ID: 7573034; Chevalier-Porst et al. 1996. PubMed ID: 8733042, Rake et al. 1999. PubMed ID: 10094563). This variant has also been referred to as 158delC/35X in the literature. This variant is interpreted as likely pathogenic or pathogenic in Clinvar (https://www.ncbi.nlm.nih.gov/clinvar/variation/21062). This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in G6PC1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(May 01, 2023)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004009790.6
First in ClinVar: Jul 16, 2023 Last updated: Apr 15, 2024 |
Comment:
G6PC1: PVS1:Strong, PM2, PM3, PP4:Moderate
Number of individuals with the variant: 1
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Pathogenic
(Jul 08, 2016)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695641.1
First in ClinVar: Aug 29, 2016 Last updated: Aug 29, 2016 |
Comment:
Variant summary: The G6PC c.79delC (p.Gln27Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent G6PC protein due to nonsense … (more)
Variant summary: The G6PC c.79delC (p.Gln27Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent G6PC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 8/121400 control chromosomes at a frequency of 0.0000659, which does not exceed the estimated maximal expected allele frequency of a pathogenic G6PC variant (0.0017321). There are multiple GSD1a patients reported in the literature who carried the variant as homozygous or heterozygous indicating the pathogenicity of the variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as Pathogenic. Taken together, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jan 04, 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: SCV000251528.16
First in ClinVar: Oct 11, 2015 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28283841, 10612834, 19541498, 23031489, 10094563, 15542400, 7573034, 34258141, 28397058, 8733042, 11739393, 19762333) (less)
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Pathogenic
(Mar 17, 2017)
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no assertion criteria provided
Method: clinical testing
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Glycogen storage disease type Ia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002093290.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953512.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963501.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000040463.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Glycogen Storage Disease Type I. | Adam MP | - | 2021 | PMID: 20301489 |
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 |
Rapid screening of 12 common mutations in Turkish GSD 1a patients using electronic DNA microarray. | Eminoglu TF | Gene | 2013 | PMID: 23352793 |
Evaluation of the biotinidase activity in hepatic glycogen storage disease patients. Undescribed genetic finding associated with atypical enzymatic behavior: an outlook. | Angaroni CJ | Journal of inherited metabolic disease | 2010 | PMID: 20532819 |
Chromosomal and genetic alterations in human hepatocellular adenomas associated with type Ia glycogen storage disease. | Kishnani PS | Human molecular genetics | 2009 | PMID: 19762333 |
Emerging therapies for glycogen storage disease type I. | Koeberl DD | Trends in endocrinology and metabolism: TEM | 2009 | PMID: 19541498 |
Elevated serum biotinidase activity in hepatic glycogen storage disorders--a convenient biomarker. | Paesold-Burda P | Journal of inherited metabolic disease | 2007 | PMID: 17994282 |
Mutation spectrum of type I glycogen storage disease in Hungary. | Miltenberger-Miltenyi G | Journal of inherited metabolic disease | 2005 | PMID: 16435186 |
Glycogen storage disease type Ia in Argentina: two novel glucose-6-phosphatase mutations affecting protein stability. | Angaroni CJ | Molecular genetics and metabolism | 2004 | PMID: 15542400 |
Glycogen storage disease type I: diagnosis and phenotype/genotype correlation. | Matern D | European journal of pediatrics | 2002 | PMID: 12373566 |
Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex. | Chou JY | Current molecular medicine | 2002 | PMID: 11949931 |
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 |
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 Ia: four novel mutations (175delGG, R170X, G266V and V338F) identified. Mutations in brief no. 220. Online. | Rake JP | Human mutation | 1999 | PMID: 10094563 |
Mutation analysis in 24 French patients with glycogen storage disease type 1a. | Chevalier-Porst F | Journal of medical genetics | 1996 | PMID: 8733042 |
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 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=G6PC | - | - | - | - |
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Text-mined citations for rs80356479 ...
HelpRecord last updated Apr 15, 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.