ClinVar Genomic variation as it relates to human health
NM_005609.4(PYGM):c.2447G>A (p.Arg816His)
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.2447G>A (p.Arg816His)
Variation ID: 95297 Accession: VCV000095297.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64746741 (GRCh38) [ NCBI UCSC ] 11: 64514213 (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 Jun 29, 2015 Aug 18, 2024 Oct 18, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005609.4:c.2447G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005600.1:p.Arg816His missense NM_001164716.1:c.2183G>A NP_001158188.1:p.Arg728His missense NC_000011.10:g.64746741C>T NC_000011.9:g.64514213C>T NG_007574.1:g.3716G>A NG_013018.1:g.18975G>A LRG_100:g.3716G>A - Protein change
- R816H, R728H
- Other names
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- Canonical SPDI
- NC_000011.10:64746740: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
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00009
The Genome Aggregation Database (gnomAD) 0.00010
The Genome Aggregation Database (gnomAD), exomes 0.00014
Exome Aggregation Consortium (ExAC) 0.00016
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
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 |
1341 | 1357 |
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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Uncertain significance (1) |
criteria provided, single submitter
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May 11, 2017 | RCV000081313.13 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Apr 6, 2018 | RCV000675627.17 | |
Uncertain significance (7) |
criteria provided, multiple submitters, no conflicts
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Oct 18, 2022 | RCV001104843.21 |
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
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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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Uncertain significance
(Sep 23, 2020)
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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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Baylor Genetics
Accession: SCV001521702.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Uncertain significance
(Jan 07, 2022)
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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: SCV002788485.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Oct 18, 2022)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003237158.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 816 of the PYGM protein (p.Arg816His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 816 of the PYGM protein (p.Arg816His). This variant is present in population databases (rs139230055, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of PYGM-related conditions (PMID: 25044680). ClinVar contains an entry for this variant (Variation ID: 95297). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Jun 04, 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:
germline
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Revvity Omics, Revvity
Accession: SCV003810425.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005191335.1
First in ClinVar: Aug 18, 2024 Last updated: Aug 18, 2024 |
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Uncertain significance
(May 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000582134.3
First in ClinVar: Jun 29, 2015 Last updated: Jun 29, 2015 |
Comment:
A variant of uncertain significance has been identified in the PYGM gene. The R816H variant has been previously reported as a homozygous change in a … (more)
A variant of uncertain significance has been identified in the PYGM gene. The R816H variant has been previously reported as a homozygous change in a consanguineous family with non-syndromic intellectual disability; additional variants were also identified and the authors concluded that the R816H only partially contributes to the phenotype in the family. (Makrythanasis et at., 2014). The R816H variant is observed in 7/16512 (0.04%) alleles from individuals of South Asian background, (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R816H variant a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. (less)
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Uncertain significance
(Apr 06, 2018)
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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: SCV000113231.8
First in ClinVar: Jan 23, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Uncertain significance
(Apr 27, 2017)
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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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Illumina Laboratory Services, Illumina
Accession: SCV001261737.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Jul 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type V
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001806523.1
First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
Sex: mixed
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Uncertain significance
(Apr 12, 2017)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000801327.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Uncertain significance
(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: SCV001461267.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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Diagnostic exome sequencing to elucidate the genetic basis of likely recessive disorders in consanguineous families. | Makrythanasis P | Human mutation | 2014 | PMID: 25044680 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PYGM | - | - | - | - |
Text-mined citations for rs139230055 ...
HelpRecord last updated Sep 29, 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.