For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile254Argfs*5) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432).
ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.759_772del (p.Ile254fs)
Germline
Classification
Help
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.
(1)
Help
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.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000546.6(TP53):c.759_772del (p.Ile254fs)
Variation ID: 2000009 Accession: VCV002000009.2
- Type and length
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Deletion, 14 bp
- Location
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Cytogenetic: 17p13.1 17: 7674191-7674204 (GRCh38) [ NCBI UCSC ] 17: 7577509-7577522 (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 Feb 8, 2023 Feb 20, 2024 Sep 9, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000546.6:c.759_772del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Ile254fs frameshift NM_001126112.3:c.759_772del NP_001119584.1:p.Ile254fs frameshift NM_001126113.3:c.759_772del NP_001119585.1:p.Ile254fs frameshift NM_001126114.3:c.759_772del NP_001119586.1:p.Ile254fs frameshift NM_001126115.2:c.363_376del NP_001119587.1:p.Ile122fs frameshift NM_001126116.2:c.363_376del NP_001119588.1:p.Ile122fs frameshift NM_001126117.2:c.363_376del NP_001119589.1:p.Ile122fs frameshift NM_001126118.2:c.642_655del NP_001119590.1:p.Ile215fs frameshift NM_001276695.3:c.642_655del NP_001263624.1:p.Ile215fs frameshift NM_001276696.3:c.642_655del NP_001263625.1:p.Ile215fs frameshift NM_001276697.3:c.282_295del NP_001263626.1:p.Ile95fs frameshift NM_001276698.3:c.282_295del NP_001263627.1:p.Ile95fs frameshift NM_001276699.3:c.282_295del NP_001263628.1:p.Ile95fs frameshift NM_001276760.3:c.642_655del NP_001263689.1:p.Ile215fs frameshift NM_001276761.3:c.642_655del NP_001263690.1:p.Ile215fs frameshift NM_001407262.1:c.759_772delCATCATCACACTGG NP_001394191.1:p.Ile254Argfs frameshift NM_001407263.1:c.642_655delCATCATCACACTGG NP_001394192.1:p.Ile215Argfs frameshift NM_001407264.1:c.759_772delCATCATCACACTGG NP_001394193.1:p.Ile254Argfs frameshift NM_001407265.1:c.642_655delCATCATCACACTGG NP_001394194.1:p.Ile215Argfs frameshift NM_001407266.1:c.759_772delCATCATCACACTGG NP_001394195.1:p.Ile254Argfs frameshift NM_001407267.1:c.642_655delCATCATCACACTGG NP_001394196.1:p.Ile215Argfs frameshift NM_001407268.1:c.759_772delCATCATCACACTGG NP_001394197.1:p.Ile254Argfs frameshift NM_001407269.1:c.642_655delCATCATCACACTGG NP_001394198.1:p.Ile215Argfs frameshift NM_001407270.1:c.759_772delCATCATCACACTGG NP_001394199.1:p.Ile254Argfs frameshift NM_001407271.1:c.642_655delCATCATCACACTGG NP_001394200.1:p.Ile215Argfs frameshift NR_176326.1:n.788_801delCATCATCACACTGG NC_000017.11:g.7674191_7674204del NC_000017.10:g.7577509_7577522del NG_017013.2:g.18347_18360del LRG_321:g.18347_18360del LRG_321t1:c.759_772del LRG_321p1:p.Ile254Argfs LRG_321t2:c.759_772del LRG_321:p.Ile254Argfs LRG_321t3:c.759_772del LRG_321p3:p.Ile254Argfs LRG_321t4:c.759_772del LRG_321p4:p.Ile254Argfs LRG_321t5:c.363_376del LRG_321p5:p.Ile122Argfs LRG_321t6:c.363_376del LRG_321p6:p.Ile122Argfs LRG_321t7:c.363_376del LRG_321p7:p.Ile122Argfs LRG_321t8:c.642_655del LRG_321p8:p.Ile215Argfs - Protein change
- I122fs, I254fs, I95fs, I215fs
- Other names
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- Canonical SPDI
- NC_000017.11:7674190:CCAGTGTGATGATG:
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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.
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- Links
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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 |
3367 | 3466 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Sep 9, 2022 | RCV002824212.3 |
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
(Sep 09, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003198825.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile254Argfs*5) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). (less)
|
Comment:
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. |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile254Argfs*5) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. | Ruijs MW | Journal of medical genetics | 2010 | PMID: 20522432 |
Text-mined citations for this variant ...
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.