ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.653T>G (p.Val218Gly)
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_000546.6(TP53):c.653T>G (p.Val218Gly)
Variation ID: 528249 Accession: VCV000528249.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 7674878 (GRCh38) [ NCBI UCSC ] 17: 7578196 (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 28, 2018 Feb 14, 2024 Oct 30, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000546.6:c.653T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Val218Gly missense NM_001126112.3:c.653T>G NP_001119584.1:p.Val218Gly missense NM_001126113.3:c.653T>G NP_001119585.1:p.Val218Gly missense NM_001126114.3:c.653T>G NP_001119586.1:p.Val218Gly missense NM_001126115.2:c.257T>G NP_001119587.1:p.Val86Gly missense NM_001126116.2:c.257T>G NP_001119588.1:p.Val86Gly missense NM_001126117.2:c.257T>G NP_001119589.1:p.Val86Gly missense NM_001126118.2:c.536T>G NP_001119590.1:p.Val179Gly missense NM_001276695.3:c.536T>G NP_001263624.1:p.Val179Gly missense NM_001276696.3:c.536T>G NP_001263625.1:p.Val179Gly missense NM_001276697.3:c.176T>G NP_001263626.1:p.Val59Gly missense NM_001276698.3:c.176T>G NP_001263627.1:p.Val59Gly missense NM_001276699.3:c.176T>G NP_001263628.1:p.Val59Gly missense NM_001276760.3:c.536T>G NP_001263689.1:p.Val179Gly missense NM_001276761.3:c.536T>G NP_001263690.1:p.Val179Gly missense NC_000017.11:g.7674878A>C NC_000017.10:g.7578196A>C NG_017013.2:g.17673T>G LRG_321:g.17673T>G LRG_321t1:c.653T>G LRG_321p1:p.Val218Gly - Protein change
- V86G, V218G, V179G, V59G
- Other names
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- Canonical SPDI
- NC_000017.11:7674877:A:C
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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
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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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TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3211 | 3306 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Oct 30, 2022 | RCV000633350.7 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jun 18, 2022 | RCV001175697.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jun 18, 2022 | RCV002289924.2 |
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
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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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Uncertain significance
(Jan 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001339404.2
First in ClinVar: Jun 22, 2020 Last updated: Jan 12, 2022 |
Comment:
This missense variant replaces valine with glycine at codon 218 of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces valine with glycine at codon 218 of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. A different missense substitution at this codon (p.Val218Met) has been classified as pathogenic (p.Val218Met, ClinVar Variation ID: 237952), suggesting this amino acid position may be functionally important. However, an experimental functional study shown this variant to have activity similar to wild-type in a yeast-based transcriptional transactivation assay (PMID: 12826609), but shows functional deficit in cell proliferation assays (PMID:29979965). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Jun 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002582033.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
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Uncertain significance
(Jun 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome 1
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002582551.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
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Uncertain significance
(Oct 30, 2022)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000754572.4
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 528249). This missense change has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 32817165). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 218 of the TP53 protein (p.Val218Gly). (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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A pedigree-based prediction model identifies carriers of deleterious de novo mutations in families with Li-Fraumeni syndrome. | Gao F | Genome research | 2020 | PMID: 32817165 |
Mutational processes shape the landscape of TP53 mutations in human cancer. | Giacomelli AO | Nature genetics | 2018 | PMID: 30224644 |
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation. | Kotler E | Molecular cell | 2018 | PMID: 29979965 |
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. | Kato S | Proceedings of the National Academy of Sciences of the United States of America | 2003 | PMID: 12826609 |
Text-mined citations for rs1555525743 ...
HelpRecord last updated Feb 14, 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.