ClinVar Genomic variation as it relates to human health
NM_000151.4(G6PC1):c.724C>T (p.Gln242Ter)
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.724C>T (p.Gln242Ter)
Variation ID: 21061 Accession: VCV000021061.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 42911076 (GRCh38) [ NCBI UCSC ] 17: 41063093 (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 Feb 14, 2024 Sep 26, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000151.4:c.724C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000142.2:p.Gln242Ter nonsense NM_001270397.2:c.*116C>T 3 prime UTR NC_000017.11:g.42911076C>T NC_000017.10:g.41063093C>T NG_011808.1:g.15279C>T LRG_147:g.15279C>T LRG_147t1:c.724C>T LRG_147p1:p.Gln242Ter NP_000142.1:p.Gln242Ter - Protein change
- Q242*
- Other names
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- Canonical SPDI
- NC_000017.11:42911075: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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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
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
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
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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/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Sep 26, 2023 | RCV000239641.15 |
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
(Jan 01, 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: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440388.1
First in ClinVar: Oct 30, 2020 Last updated: Oct 30, 2020 |
Comment:
This variant was identified as compound heterozygous.
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Pathogenic
(May 23, 2022)
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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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Fulgent Genetics, Fulgent Genetics
Accession: SCV002798616.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(Dec 20, 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: SCV001194047.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 03, 2020 |
Comment:
NM_000151.3(G6PC):c.724C>T(Q242*) is classified as likely pathogenic in the context of glycogen storage disease type Ia. Sources cited for classification include the following: 12373566, 19762333, 10834516, … (more)
NM_000151.3(G6PC):c.724C>T(Q242*) is classified as likely pathogenic in the context of glycogen storage disease type Ia. Sources cited for classification include the following: 12373566, 19762333, 10834516, 7573034 and 23046672. Classification of NM_000151.3(G6PC):c.724C>T(Q242*) is based on the following criteria: This variant 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)
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Pathogenic
(Sep 26, 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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Invitae
Accession: SCV002510567.3
First in ClinVar: May 16, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln242*) in the G6PC gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Gln242*) in the G6PC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 116 amino acid(s) of the G6PC protein. This variant is present in population databases (rs80356485, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with G6PC-related conditions (PMID: 7573034). ClinVar contains an entry for this variant (Variation ID: 21061). This variant disrupts a region of the G6PC protein in which other variant(s) (p.Gln347*) have been determined to be pathogenic (PMID: 7573034, 8182131, 8733042, 10070617, 11949931, 28397058). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (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: SCV001163789.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
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Pathogenic
(Mar 30, 2020)
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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: SCV001339196.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: G6PC c.724C>T (p.Gln242X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: G6PC c.724C>T (p.Gln242X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 251396 control chromosomes (gnomAD). c.724C>T has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ia (Lei_1995, Calderaro_2012, Matern_2002). 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, however, does not allow convincing conclusions about the variant effect. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (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: SCV002093321.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Pathogenic
(Aug 25, 2016)
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no assertion criteria 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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National Center for Biotechnology Information, National Institutes of Health
Accession: SCV000298097.1
First in ClinVar: Aug 29, 2016 Last updated: Aug 29, 2016
Comment:
Originally appeared in GeneReview for 'Glycogen Storage Disease Type I'; deleted from update of 8/25/2016.
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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 |
Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I. | Calderaro J | Journal of hepatology | 2013 | PMID: 23046672 |
Chromosomal and genetic alterations in human hepatocellular adenomas associated with type Ia glycogen storage disease. | Kishnani PS | Human molecular genetics | 2009 | PMID: 19762333 |
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 |
Molecular genetics of type 1 glycogen storage disease. | Janecke AR | Molecular genetics and metabolism | 2001 | PMID: 11386847 |
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 |
Mutations in the glucose-6-phosphatase gene of 53 Italian patients with glycogen storage disease type Ia. | Stroppiano M | Journal of inherited metabolic disease | 1999 | PMID: 10070617 |
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 |
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Text-mined citations for rs80356485 ...
HelpRecord last updated May 08, 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.