ClinVar Genomic variation as it relates to human health
NM_000642.3(AGL):c.18_19del (p.Gln6fs)
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_000642.3(AGL):c.18_19del (p.Gln6fs)
Variation ID: 195097 Accession: VCV000195097.32
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 1p21.2 1: 99851059-99851060 (GRCh38) [ NCBI UCSC ] 1: 100316615-100316616 (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 Apr 4, 2013 Feb 20, 2024 Jan 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000642.3:c.18_19del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000633.2:p.Gln6fs frameshift NM_000642.3:c.18_19delGA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_000028.3:c.18_19delGA NP_000019.2:p.Gln6Hisfs frameshift NM_000642.2:c.17_18delAG NM_000643.3:c.18_19delGA NP_000634.2:p.Gln6Hisfs frameshift NM_000644.3:c.18_19delGA NP_000635.2:p.Gln6Hisfs frameshift NM_000646.3:c.-174_-173delGA NM_001425325.1:c.18_19delGA NP_001412254.1:p.Gln6Hisfs frameshift NM_001425326.1:c.18_19delGA NP_001412255.1:p.Gln6Hisfs frameshift NM_001425327.1:c.18_19delGA NP_001412256.1:p.Gln6Hisfs frameshift NM_001425328.1:c.18_19delGA NP_001412257.1:p.Gln6Hisfs frameshift NM_001425329.1:c.18_19delGA NP_001412258.1:p.Gln6Hisfs frameshift NM_001425332.1:c.18_19delGA NP_001412261.1:p.Gln6Hisfs frameshift NC_000001.11:g.99851060_99851061del NC_000001.10:g.100316616_100316617del NG_012865.1:g.5977_5978del NG_091707.1:g.679_680del - Protein change
- Q6fs
- Other names
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- Canonical SPDI
- NC_000001.11:99851058:AGA:A
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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
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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
Help
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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AGL | - | - |
GRCh38 GRCh37 |
2635 | 2654 |
Conditions - Germline
Condition
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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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (2) |
criteria provided, single submitter
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Mar 30, 2017 | RCV000001155.4 | |
Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Jan 16, 2024 | RCV000175637.27 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 9, 2021 | RCV000723819.7 |
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
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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
(Mar 30, 2017)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease IIIb
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697529.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
Comment:
Variant summary: The AGL c.18_19delGA (p.Gln6Hisfs) variant results in a premature termination codon, predicted to cause a truncated or absent AGL protein due to nonsense … (more)
Variant summary: The AGL c.18_19delGA (p.Gln6Hisfs) variant results in a premature termination codon, predicted to cause a truncated or absent AGL 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 (e.g. c.3216_3217delGA/p.Glu1072fs). This variant is absent from 121356 control chromosomes (ExAC dataset). This variant has been reported homozygously and in compound heterozygosity in patients with clinically and biochemically confirmed dx of GSD IIIb (Goldstein_GeneticsMed_2010). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely pathogenic/pathogenic". Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Jun 13, 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: SCV000227163.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Sex: mixed
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Likely pathogenic
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000346051.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The AGL c.18_19delGA (p.Gln6HisfsTer20) variant, also referred to as c.17_18delAG, results in a frameshift, and is predicted to result in premature termination of the protein. … (more)
The AGL c.18_19delGA (p.Gln6HisfsTer20) variant, also referred to as c.17_18delAG, results in a frameshift, and is predicted to result in premature termination of the protein. The p.Gln6HisfsTer20 variant has been reported in at least three studies in which it is found in a total of 17 patients with glycogen storage disease type III, including in one in a homozygous state, in three in a compound heterozygous state, and in 13 in a heterozygous state where a second variant was not identified (Shen et al. 1996; Goldstein et al. 2010; Hobson-Webb et al. 2010). The p.Gln6HisfsTer20 variant was absent from 20 controls, but is reported at a frequency of 0.00009 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence and the potential impact of frameshift variants, the p.Gln6HisfsTer20 variant is classified as likely pathogenic for glycogen storage disease type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Likely pathogenic
(Dec 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001194065.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 03, 2020 |
Comment:
NM_000642.2(AGL):c.18_19delGA(Q6Hfs*20) is classified as likely pathogenic in the context of glycogen storage disease type III. Sources cited for classification include the following: PMID 20648714 and … (more)
NM_000642.2(AGL):c.18_19delGA(Q6Hfs*20) is classified as likely pathogenic in the context of glycogen storage disease type III. Sources cited for classification include the following: PMID 20648714 and 8755644. Classification of NM_000642.2(AGL):c.18_19delGA(Q6Hfs*20) 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
(Sep 18, 2017)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease iii
Affected status: unknown
Allele origin:
germline
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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448994.1
First in ClinVar: Dec 11, 2020 Last updated: Dec 11, 2020 |
Number of individuals with the variant: 1
Clinical Features:
Intellectual disability (present) , Movement disorder (present) , Cerebral palsy (present) , Involuntary movements (present) , Rhabdomyolysis (present) , Progressive spastic quadriplegia (present) , Spastic … (more)
Intellectual disability (present) , Movement disorder (present) , Cerebral palsy (present) , Involuntary movements (present) , Rhabdomyolysis (present) , Progressive spastic quadriplegia (present) , Spastic gait (present) , Chorea (present) , Elevated serum creatine phosphokinase (present) , Spastic diplegia (present) , Abnormality of nervous system physiology (present) , Choreoathetosis (present) , Brain atrophy (present) , Failure to thrive (present) , Susceptibility to herpesvirus (present) , Hyperkinesis (present) , Abnormality of the cerebral white matter (present) , Constipation (present) (less)
Sex: female
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Pathogenic
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002055456.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Pathogenic
(Feb 09, 2021)
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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: SCV003761773.2
First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023 |
Comment:
Not observed at a significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a … (more)
Not observed at a significant frequency in large population cohorts (gnomAD); 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: 34820282, 20648714, 30487145, 20301788, 20526204, 20490926, 20071996, 8755644, 31263214, 32222031, 33368379, 31589614) (less)
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Pathogenic
(Oct 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004214387.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000939193.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln6Hisfs*20) in the AGL gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln6Hisfs*20) in the AGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). This variant is present in population databases (rs113994127, gnomAD 0.008%). This premature translational stop signal has been observed in individuals with glycogen storage disease III (PMID: 8755644, 20490926, 20648714). ClinVar contains an entry for this variant (Variation ID: 195097). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 15, 1996)
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no assertion criteria provided
Method: literature only
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GLYCOGEN STORAGE DISEASE, TYPE IIIb
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000021305.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 23, 2020 |
Comment on evidence:
In 10 of 13 patients with GSD IIIb (GSD3B; 232400), Shen et al. (1996) identified a 2-bp deletion (c.17_18delAG) in the AGL gene, resulting in … (more)
In 10 of 13 patients with GSD IIIb (GSD3B; 232400), Shen et al. (1996) identified a 2-bp deletion (c.17_18delAG) in the AGL gene, resulting in a truncated protein. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001454492.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Glycogen storage disease type III
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000040762.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
Comment:
Associated with GSD IIIb phenotype
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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 III. | Adam MP | - | 2022 | PMID: 20301788 |
Molecular analysis of the AGL gene: identification of 25 novel mutations and evidence of genetic heterogeneity in patients with Glycogen Storage Disease Type III. | Goldstein JL | Genetics in medicine : official journal of the American College of Medical Genetics | 2010 | PMID: 20648714 |
Echocardiographic manifestations of Glycogen Storage Disease III: increase in wall thickness and left ventricular mass over time. | Vertilus SM | Genetics in medicine : official journal of the American College of Medical Genetics | 2010 | PMID: 20526204 |
Glycogen storage disease type III in the Irish population. | Crushell E | Journal of inherited metabolic disease | 2010 | PMID: 20490926 |
The electrodiagnostic characteristics of Glycogen Storage Disease Type III. | Hobson-Webb LD | Genetics in medicine : official journal of the American College of Medical Genetics | 2010 | PMID: 20071996 |
Distinct mutations in the glycogen debranching enzyme found in glycogen storage disease type III lead to impairment in diverse cellular functions. | Cheng A | Human molecular genetics | 2009 | PMID: 19299494 |
Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle. | Shen J | The Journal of clinical investigation | 1996 | PMID: 8755644 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=AGL | - | - | - | - |
Text-mined citations for rs113994127 ...
HelpRecord last updated Feb 28, 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.