ClinVar Genomic variation as it relates to human health
NM_005609.4(PYGM):c.1948C>T (p.Arg650Ter)
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.1948C>T (p.Arg650Ter)
Variation ID: 433147 Accession: VCV000433147.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64751346 (GRCh38) [ NCBI UCSC ] 11: 64518818 (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 20, 2017 Feb 14, 2024 Jul 25, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005609.4:c.1948C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005600.1:p.Arg650Ter nonsense NM_001164716.1:c.1684C>T NP_001158188.1:p.Arg562Ter nonsense NM_005609.3:c.[1948C>T] NC_000011.10:g.64751346G>A NC_000011.9:g.64518818G>A NG_013018.1:g.14370C>T - Protein change
- R650*, R562*
- Other names
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- Canonical SPDI
- NC_000011.10:64751345: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
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
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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PYGM | - | - |
GRCh38 GRCh37 |
1315 | 1329 |
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 (5) |
criteria provided, multiple submitters, no conflicts
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Jul 25, 2023 | RCV000498994.19 | |
Likely pathogenic (1) |
no assertion criteria provided
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Jul 28, 2023 | RCV003324712.7 |
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
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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
(Jan 12, 2016)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type V
Affected status: yes
Allele origin:
unknown
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Molecular Diagnostics Lab, Nemours Children's Health, Delaware
Accession: SCV000590833.1
First in ClinVar: Aug 20, 2017 Last updated: Aug 20, 2017 |
Age: 40-49 years
Sex: male
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type V
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002073185.1
First in ClinVar: Feb 03, 2022 Last updated: Feb 03, 2022 |
Comment:
The stop gained p.R650* in PYGM (NM_005609.4) has been previously reported in affected individuals (Aquaron R et al,Bruno C et al). It has been submitted … (more)
The stop gained p.R650* in PYGM (NM_005609.4) has been previously reported in affected individuals (Aquaron R et al,Bruno C et al). It has been submitted to ClinVar as Pathogenic. The p.R650* variant is observed in 1/18,392 (0.0054%) alleles from individuals of East Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function mutations have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Exercise intolerance (present) , Elevated circulating creatine kinase concentration (present) , Polyneuropathy (present) , Abnormality of the mitochondrion (present) , Myopathy (present)
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Pathogenic
(Jul 13, 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: SCV004207252.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jul 25, 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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Invitae
Accession: SCV001198745.5
First in ClinVar: Apr 15, 2020 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: 433147). 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: 433147). This premature translational stop signal has been observed in individuals with glycogen storage disease type V (PMID: 17324573; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg650*) in the PYGM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PYGM are known to be pathogenic (PMID: 8316268, 16786513). (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 V
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001461272.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Likely pathogenic
(Jul 28, 2023)
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no assertion criteria provided
Method: clinical testing
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see cases
Affected status: yes
Allele origin:
unknown
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Gene Friend Way, National Innovation Center
Accession: SCV004013896.2
First in ClinVar: Jul 22, 2023 Last updated: Aug 30, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg650*) in the PYGM gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg650*) in the PYGM gene. It is expected to result in an absent or disrupted protein product. This premature translational stop signal has been observed in individuals with glycogen storage disease type V (PMID: 17324573). Recent genetic and functional studies have identified a role of abnormal glycinergic signaling in Autism Spectrum Disorder (ASD) (PMID: 28270747). In our study, a child diagnosed with ASD is the carrier of this mutation and also PRNP (rs1799990). (less)
Number of individuals with the variant: 1
Clinical Features:
Autistic behavior (present)
Method: 800K direct targets snp array, validated with Sanger sequencing
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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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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 |
Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease). | Tsujino S | The New England journal of medicine | 1993 | PMID: 8316268 |
Text-mined citations for rs114073621 ...
HelpRecord last updated Apr 20, 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.