ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.642T>G (p.His214Gln)
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.
Uncertain significance(3); Likely benign(6)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000546.6(TP53):c.642T>G (p.His214Gln)
Variation ID: 140943 Accession: VCV000140943.64
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 7674889 (GRCh38) [ NCBI UCSC ] 17: 7578207 (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 Jan 6, 2017 Feb 20, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000546.6:c.642T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.His214Gln missense NM_001126112.3:c.642T>G NP_001119584.1:p.His214Gln missense NM_001126113.3:c.642T>G NP_001119585.1:p.His214Gln missense NM_001126114.3:c.642T>G NP_001119586.1:p.His214Gln missense NM_001126115.2:c.246T>G NP_001119587.1:p.His82Gln missense NM_001126116.2:c.246T>G NP_001119588.1:p.His82Gln missense NM_001126117.2:c.246T>G NP_001119589.1:p.His82Gln missense NM_001126118.2:c.525T>G NP_001119590.1:p.His175Gln missense NM_001276695.3:c.525T>G NP_001263624.1:p.His175Gln missense NM_001276696.3:c.525T>G NP_001263625.1:p.His175Gln missense NM_001276697.3:c.165T>G NP_001263626.1:p.His55Gln missense NM_001276698.3:c.165T>G NP_001263627.1:p.His55Gln missense NM_001276699.3:c.165T>G NP_001263628.1:p.His55Gln missense NM_001276760.3:c.525T>G NP_001263689.1:p.His175Gln missense NM_001276761.3:c.525T>G NP_001263690.1:p.His175Gln missense NC_000017.11:g.7674889A>C NC_000017.10:g.7578207A>C NG_017013.2:g.17662T>G LRG_321:g.17662T>G LRG_321t1:c.642T>G LRG_321p1:p.His214Gln P04637:p.His214Gln - Protein change
- H175Q, H214Q, H82Q, H55Q
- Other names
- p.H214Q:CAT>CAG
- Canonical SPDI
- NC_000017.11:7674888: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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD) 0.00004
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
Help
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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TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3211 | 3306 |
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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Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 10, 2022 | RCV000129218.19 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV000195927.25 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Apr 11, 2023 | RCV000410083.11 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Apr 16, 2021 | RCV001283869.15 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 15, 2023 | RCV002267869.12 |
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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Likely benign
(Dec 11, 2017)
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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: SCV000911487.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
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Likely benign
(Feb 10, 2022)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002530478.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Likely benign
(Jul 27, 2018)
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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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Ambry Genetics
Accession: SCV000183969.8
First in ClinVar: Aug 06, 2014 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Jan 22, 2016)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000488187.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Uncertain significance
(Apr 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469325.3
First in ClinVar: Jan 26, 2021 Last updated: Dec 31, 2022 |
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Likely benign
(May 23, 2018)
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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: SCV000211753.9
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 14559903, 23259501, 16728565, 15781620, 29979965, 31321604)
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Uncertain significance
(Apr 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004017885.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
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Likely benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002551025.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
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Likely benign
(Jan 31, 2024)
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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: SCV000253315.11
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
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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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TP53 variants of uncertain significance: increasing challenges in variant interpretation and genetic counseling. | Bittar CM | Familial cancer | 2019 | PMID: 31321604 |
Lack of correlation between p53-dependent transcriptional activity and the ability to induce apoptosis among 179 mutant p53s. | Kakudo Y | Cancer research | 2005 | PMID: 15781620 |
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 rs587781386 ...
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.