ClinVar Genomic variation as it relates to human health
NM_005609.4(PYGM):c.280C>T (p.Arg94Trp)
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_005609.4(PYGM):c.280C>T (p.Arg94Trp)
Variation ID: 456518 Accession: VCV000456518.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64758668 (GRCh38) [ NCBI UCSC ] 11: 64526140 (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 Dec 26, 2017 Feb 20, 2024 Jan 30, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005609.4:c.280C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005600.1:p.Arg94Trp missense NM_001164716.1:c.244-402C>T intron variant NC_000011.10:g.64758668G>A NC_000011.9:g.64526140G>A NG_013018.1:g.7048C>T - Protein change
- R94W
- Other names
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- Canonical SPDI
- NC_000011.10:64758667:G: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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00004
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
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
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. |
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PYGM | - | - |
GRCh38 GRCh37 |
1315 | 1329 |
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. |
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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 30, 2024 | RCV000557171.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 18, 2019 | RCV001540069.2 |
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
(Apr 18, 2019)
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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: SCV001757907.1
First in ClinVar: Jul 24, 2021 Last updated: Jul 24, 2021 |
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports … (more)
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect This variant is associated with the following publications: (PMID: 22347505, 19472443, 29143597, 21802952, 17994553, 17324573, 16786513, 17221871, 12508303, 30316539) (less)
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Pathogenic
(Sep 12, 2021)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type V
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002809786.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Aug 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type V
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004207240.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Aug 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type V
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002019573.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 30, 2024)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type V
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000626785.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 94 of the PYGM protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 94 of the PYGM protein (p.Arg94Trp). This variant is present in population databases (rs370247862, gnomAD 0.006%). This missense change has been observed in individual(s) with McArdle disease (glycogen storage disease type V) (PMID: 12508303, 16786513, 17324573, 17404776, 19472443, 21802952, 22250184). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 456518). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PYGM protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PYGM function (PMID: 12508303, 17324573, 17404776, 17994553, 22250184). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 10, 2021)
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no assertion criteria provided
Method: clinical testing
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Glycogen storage disease V
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002092348.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 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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Genotypic and phenotypic features of McArdle disease: insights from the Spanish national registry. | Lucia A | Journal of neurology, neurosurgery, and psychiatry | 2012 | PMID: 22250184 |
Molecular and clinical study of McArdle's disease in a cohort of 123 European patients. Identification of 20 novel mutations. | Vieitez I | Neuromuscular disorders : NMD | 2011 | PMID: 21802952 |
High-resolution melting facilitates mutation screening of PYGM in patients with McArdle disease. | Duno M | Annals of human genetics | 2009 | PMID: 19472443 |
Expression of the muscle glycogen phosphorylase gene in patients with McArdle disease: the role of nonsense-mediated mRNA decay. | Nogales-Gadea G | Human mutation | 2008 | PMID: 17994553 |
Analysis of spectrum and frequencies of mutations in McArdle disease. Identification of 13 novel mutations. | Deschauer M | Journal of neurology | 2007 | PMID: 17404776 |
Molecular characterization of myophosphorylase deficiency (McArdle disease) in 34 patients from Southern France: identification of 10 new mutations. Absence of genotype-phenotype correlation. | Aquaron R | Neuromuscular disorders : NMD | 2007 | PMID: 17324573 |
McArdle disease: the mutation spectrum of PYGM in a large Italian cohort. | Bruno C | Human mutation | 2006 | PMID: 16786513 |
Two novel mutations in the myophosphorylase gene in a patient with McArdle disease. | Deschauer M | Muscle & nerve | 2003 | PMID: 12508303 |
Text-mined citations for rs370247862 ...
HelpRecord last updated Mar 17, 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.