ClinVar Genomic variation as it relates to human health
NM_000152.5(GAA):c.340_341insT (p.Lys114fs)
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_000152.5(GAA):c.340_341insT (p.Lys114fs)
Variation ID: 1068640 Accession: VCV001068640.10
- Type and length
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Insertion, 1 bp
- Location
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Cytogenetic: 17q25.3 17: 80104926-80104927 (GRCh38) [ NCBI UCSC ] 17: 78078725-78078726 (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 May 10, 2021 Feb 14, 2024 Oct 25, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000152.5:c.340_341insT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000143.2:p.Lys114fs frameshift NM_001079803.3:c.340_341insT NP_001073271.1:p.Lys114fs frameshift NM_001079804.3:c.340_341insT NP_001073272.1:p.Lys114fs frameshift NC_000017.11:g.80104926_80104927insT NC_000017.10:g.78078725_78078726insT NG_009822.1:g.8371_8372insT LRG_673:g.8371_8372insT LRG_673t1:c.340_341insT - Protein change
- K114fs
- Other names
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- Canonical SPDI
- NC_000017.11:80104926::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.
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- Links
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
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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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GAA | - | - |
GRCh38 GRCh38 GRCh37 |
2757 | 2807 |
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
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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 (3) |
criteria provided, multiple submitters, no conflicts
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Oct 25, 2023 | RCV001380266.15 |
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
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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
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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 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type II
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004122098.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
Variant summary: GAA c.340_341insT (p.Lys114IlefsX32) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: GAA c.340_341insT (p.Lys114IlefsX32) 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. The variant was absent in 247738 control chromosomes. c.340_341insT has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) (e.g. Hamdan_2010). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 20821053). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Apr 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type II
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004197839.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type II
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001578264.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1068640). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1068640). This premature translational stop signal has been observed in individual(s) with Pompe disease (PMID: 14695532, 22252923). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys114Ilefs*32) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience. | Bali DS | American journal of medical genetics. Part C, Seminars in medical genetics | 2012 | PMID: 22252923 |
Antenatal diagnosis of pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy. | Hamdan MA | Journal of inherited metabolic disease | 2010 | PMID: 20821053 |
Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. | Kroos M | Human mutation | 2008 | PMID: 18425781 |
Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II. | Hermans MM | Human mutation | 2004 | PMID: 14695532 |
Text-mined citations for rs2143827701 ...
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.