ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.751A>C (p.Ile251Leu)
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
-
NM_000546.6(TP53):c.751A>C (p.Ile251Leu)
Variation ID: 182937 Accession: VCV000182937.10
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17p13.1 17: 7674212 (GRCh38) [ NCBI UCSC ] 17: 7577530 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 9, 2016 Nov 29, 2022 Jun 18, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000546.6:c.751A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Ile251Leu missense NM_001126112.3:c.751A>C NP_001119584.1:p.Ile251Leu missense NM_001126113.3:c.751A>C NP_001119585.1:p.Ile251Leu missense NM_001126114.3:c.751A>C NP_001119586.1:p.Ile251Leu missense NM_001126115.2:c.355A>C NP_001119587.1:p.Ile119Leu missense NM_001126116.2:c.355A>C NP_001119588.1:p.Ile119Leu missense NM_001126117.2:c.355A>C NP_001119589.1:p.Ile119Leu missense NM_001126118.2:c.634A>C NP_001119590.1:p.Ile212Leu missense NM_001276695.3:c.634A>C NP_001263624.1:p.Ile212Leu missense NM_001276696.3:c.634A>C NP_001263625.1:p.Ile212Leu missense NM_001276697.3:c.274A>C NP_001263626.1:p.Ile92Leu missense NM_001276698.3:c.274A>C NP_001263627.1:p.Ile92Leu missense NM_001276699.3:c.274A>C NP_001263628.1:p.Ile92Leu missense NM_001276760.3:c.634A>C NP_001263689.1:p.Ile212Leu missense NM_001276761.3:c.634A>C NP_001263690.1:p.Ile212Leu missense NC_000017.11:g.7674212T>G NC_000017.10:g.7577530T>G NG_017013.2:g.18339A>C LRG_321:g.18339A>C LRG_321t1:c.751A>C LRG_321p1:p.Ile251Leu P04637:p.Ile251Leu - Protein change
- I119L, I212L, I251L, I92L
- Other names
- p.I251L:ATC>CTC
- Canonical SPDI
- NC_000017.11:7674211:T:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- probably has functional consequence
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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. |
|||
TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3211 | - |
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/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 25, 2018 | RCV000161037.6 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 18, 2022 | RCV000492548.5 | |
Likely pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2018 | RCV000785277.4 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
- | RCV002280104.3 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Jun 18, 2022 | RCV002288694.3 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(May 27, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000211759.10
First in ClinVar: Feb 24, 2015 Last updated: Oct 09, 2016 |
Comment:
The I251L (ATC>CTC) missense variant in the TP53 gene, denoted c.751A>C at the cDNA level, has been reported previously in association with Li-Fraumeni syndrome (Wu … (more)
The I251L (ATC>CTC) missense variant in the TP53 gene, denoted c.751A>C at the cDNA level, has been reported previously in association with Li-Fraumeni syndrome (Wu et al., 2011). Additionally, the NHLBI ESP Exome Variant Server reports I251L was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Therefore, I251L is interpreted as a disease-causing variant. (less)
|
|
Likely pathogenic
(Jun 25, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
somatic
|
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449920.1
First in ClinVar: Dec 11, 2020 Last updated: Dec 11, 2020 |
Number of individuals with the variant: 1
|
|
Likely pathogenic
(-)
|
criteria provided, single submitter
(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Method: research
|
Gastric cancer
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
|
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002568061.1
First in ClinVar: Sep 03, 2022 Last updated: Sep 03, 2022 |
Comment:
No evidence was found for rs730882007 (p.I251L) TP53 gene variant in stomach cancer so far. However, this variant has been observed in a male patient … (more)
No evidence was found for rs730882007 (p.I251L) TP53 gene variant in stomach cancer so far. However, this variant has been observed in a male patient suffering from carcinoma of the stomach and in addition, this alteration is predicted to be deleterious by in silico analysis. (less)
Clinical Features:
Abdominal pain (present)
Age: 40-49 years
Sex: male
Ethnicity/Population group: Indian
Geographic origin: Asia
Method: Targeted gene sequencing is a useful tool for analyzing specific mutations in a given sample. Specific genes suspected to have associations with the disease or phenotype are studied.
Testing laboratory: Org:507246
Testing laboratory interpretation: Likely pathogenic
|
|
Likely pathogenic
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002582360.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
|
Likely pathogenic
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002583020.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
|
Likely pathogenic
(Dec 08, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000581167.5
First in ClinVar: Jul 01, 2017 Last updated: Nov 29, 2022 |
Comment:
The p.I251L variant (also known as c.751A>C), located in coding exon 6 of the TP53 gene, results from an A to C substitution at nucleotide … (more)
The p.I251L variant (also known as c.751A>C), located in coding exon 6 of the TP53 gene, results from an A to C substitution at nucleotide position 751. The isoleucine at codon 251 is replaced by leucine, an amino acid with highly similar properties. This alteration has been reported in the literature in one family with Li-Fraumeni syndrome (Wu CC et al. Hum. Genet. 2011 Jun; 129(6):663-73). This alteration is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation capacity (Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
Number of individuals with the variant: 1
|
|
Likely pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Neoplasm of ovary
Affected status: yes
Allele origin:
somatic
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923845.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
|
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
---|---|---|---|---|
probably has functional consequence
|
|
|
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002568061.1
|
|
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
A novel genomic classification system of gastric cancer via integrating multidimensional genomic characteristics. | Wang H | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association | 2021 | PMID: 34095982 |
Joint effects of germ-line TP53 mutation, MDM2 SNP309, and gender on cancer risk in family studies of Li-Fraumeni syndrome. | Wu CC | Human genetics | 2011 | PMID: 21305319 |
Transcriptional functionality of germ line p53 mutants influences cancer phenotype. | Monti P | Clinical cancer research : an official journal of the American Association for Cancer Research | 2007 | PMID: 17606709 |
Text-mined citations for rs730882007 ...
HelpRecord last updated Apr 15, 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.