chr17:7674221:G>A Detail (hg38) (TP53)

Information

Genome

Assembly Position
hg19 chr17:7,577,539-7,577,539 View the variant detail on this assembly version.
hg38 chr17:7,674,221-7,674,221

HGVS

Type Transcript Protein
RefSeq NM_000546.5:c.742C>T NP_000537.3:p.Arg248Trp
NM_001126112.2:c.742C>T NP_001119584.1:p.Arg248Trp
NM_001276760.1:c.742C>T NP_001263689.1:p.Arg248Trp
Summary

MGeND

Clinical significance Likely pathogenic Pathogenic not provided
Variant entry 4
GWAS entry
Disease area statistics Show details

Frequency

JP HGVD:[No Data.]
ToMMo:[No Data.]
NCBN:[No Data.]
NCBN(Hondo):[No Data.]
NCBN(Ryukyu):[No Data.]
East asia ExAC:<0.001

Prediction

ClinVar

Clinical Significance Pathogenic
Review star
Show details
Links
Type Database ID Link
Gene MIM 191170 OMIM
HGNC 11998 HGNC
Ensembl ENSG00000141510 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC COSM3388183 COSMIC
MONDO
Disease area statistics
MGeND
Clinical significance Last evaluated Condition Origin Submission ID Submitter Institute Citation Comment Image
Pathogenic 2017/10/19 lung adenocarcinoma somatic MGS000017
(TMGS000052) 		Kohei Miyazono Tokyo University
Likely pathogenic 2017/07/06 small cell lung cancer somatic MGS000017
(TMGS000052) 		Kohei Miyazono Tokyo University
not provided 2018/04/26 squamous cell carcinoma of the hypopharynx somatic MGS000017
(TMGS000052) 		Kohei Miyazono Tokyo University
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Pathogenic 2023-10-13 criteria provided, multiple submitters, no conflicts Li-Fraumeni syndrome 1 unknown germline Detail
Pathogenic 2023-12-12 criteria provided, multiple submitters, no conflicts Hereditary cancer-predisposing syndrome germline Detail
Pathogenic 2019-08-28 reviewed by expert panel Li-Fraumeni syndrome unknown germline Detail
Pathogenic 2022-05-11 criteria provided, multiple submitters, no conflicts not provided unknown germline Detail
Likely pathogenic 2016-05-31 no assertion criteria provided acute myeloid leukemia somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided lung adenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided glioblastoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Small cell lung carcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Squamous cell carcinoma of the head and neck somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided B-cell chronic lymphocytic leukemia somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided ovarian serous cystadenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided myelodysplastic syndrome somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided prostate adenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Breast neoplasm somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Carcinoma of esophagus somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided gastric adenocarcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided multiple myeloma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided uterine carcinosarcoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Neoplasm of brain somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Squamous cell lung carcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided hepatocellular carcinoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided somatic Detail
Likely pathogenic 2015-07-14 no assertion criteria provided Neoplasm somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Neoplasm of the large intestine somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided medulloblastoma somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Malignant neoplasm of body of uterus somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Malignant melanoma of skin somatic Detail
Likely pathogenic 2016-05-31 no assertion criteria provided pancreatic adenocarcinoma somatic Detail
Pathogenic criteria provided, single submitter Pectus excavatum,acute myeloid leukemia,Cognitive impairment germline Detail
Pathogenic criteria provided, single submitter Pectus excavatum,acute myeloid leukemia,Cognitive impairment germline Detail
Pathogenic criteria provided, single submitter Pectus excavatum,acute myeloid leukemia,Cognitive impairment germline Detail
Pathogenic Likely pathogenic 2021-03-19 no assertion criteria provided Neoplasm of ovary somatic Detail
Pathogenic 2019-04-30 no assertion criteria provided Lip and oral cavity carcinoma somatic Detail
Pathogenic 2020-12-22 no assertion criteria provided choroid plexus carcinoma germline Detail
Uncertain significance 2020-10-30 no assertion criteria provided gallbladder cancer somatic Detail
Pathogenic 2022-05-10 no assertion criteria provided congenital fibrosarcoma somatic Detail
Pathogenic 2021-09-07 criteria provided, single submitter Breast and/or ovarian cancer germline Detail
Pathogenic 2021-07-01 no assertion criteria provided Gastric cancer germline Detail
Pathogenic 2023-07-25 no assertion criteria provided Malignant lymphoma, large B-cell, diffuse somatic Detail
Pathogenic 2023-09-27 criteria provided, single submitter Adrenocortical carcinoma, hereditary unknown Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
breast cancer B Prognostic Supports Poor Outcome Somatic 3 16489069 Detail
cancer AMGMDS3 D Predictive Supports Resistance Somatic 4 25730903 Detail
DisGeNET
Score Disease name Description Source Pubmed Links
0.080 Carcinoma of lung Mutant p53 R248Q but not R248W enhances in vitro invasiveness of human lung canc... BeFree 21187651 Detail
0.441 Li-Fraumeni syndrome 1 NA CLINVAR Detail
0.160 Malignant neoplasm of lung Mutant p53 R248Q but not R248W enhances in vitro invasiveness of human lung canc... BeFree 21187651 Detail
0.122 Neoplastic Syndromes, Hereditary NA CLINVAR Detail
0.369 Li-Fraumeni syndrome NA CLINVAR Detail
0.157 pancreatic carcinoma Using the whole-cell recording mode of the patch-clamp technique, functional ion... BeFree 14978241 Detail
0.012 Tumors of Adrenal Cortex Composite adrenal anaplastic neuroblastoma and virilizing adrenocortical tumor w... BeFree 17427234 Detail
0.007 Lichen Sclerosus et Atrophicus In matched samples, immunohistochemistry evaluation of p53 protein expression re... BeFree 17554370 Detail
0.067 colon carcinoma To elucidate whether and how mutant p53 acquires its gain-of-function, mutant p5... BeFree 18701504 Detail
0.369 Li-Fraumeni syndrome Here, we report a family with LFS harboring a germline TP53 mutation (R248W) loc... BeFree 19378321 Detail
0.002 pancreatic carcinoma Using the whole-cell recording mode of the patch-clamp technique, functional ion... BeFree 14978241 Detail
0.369 Li-Fraumeni syndrome We report a patient with composite neuroblastoma (NB), adrenocortical tumor (ACT... BeFree 17427234 Detail
0.001 Squamous cell carcinoma of pharynx Using short hairpin RNA against p53, transient ectopic expression of wild-type p... BeFree 21308745 Detail
<0.001 Glioma Overexpression of the paradigmatic p53 mutants p53(R175H), p53(R248W) and p53(R2... BeFree 18202704 Detail
0.039 Malignant neoplasm of pancreas Using the whole-cell recording mode of the patch-clamp technique, functional ion... BeFree 14978241 Detail
0.002 Malignant neoplasm of pancreas Using the whole-cell recording mode of the patch-clamp technique, functional ion... BeFree 14978241 Detail
<0.001 Anaplastic thyroid carcinoma Adoptive overexpression of wild-type p53, but not of its inactive (R248W and R27... BeFree 15899946 Detail
0.059 Malignant tumor of colon To elucidate whether and how mutant p53 acquires its gain-of-function, mutant p5... BeFree 18701504 Detail
0.127 neuroblastoma Composite adrenal anaplastic neuroblastoma and virilizing adrenocortical tumor w... BeFree 17427234 Detail
0.037 Central neuroblastoma Composite adrenal anaplastic neuroblastoma and virilizing adrenocortical tumor w... BeFree 17427234 Detail
Annotation

Annotations

DescrptionSourceLinks
In breast cancer patients harboring R248W mutation, the prognosis is worse than any other hotspot TP... CIViC Evidence Detail
Subset of 58 cancer cell lines with unaltered TP53 is sensitive to MDM2 Inhibitor AMGMDS3. None of 1... CIViC Evidence Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Li-Fraumeni syndrome 1 ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Hereditary cancer-predisposing syndrome ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Li-Fraumeni syndrome ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND not provided ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Acute myeloid leukemia ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Lung adenocarcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Glioblastoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Small cell lung carcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Squamous cell carcinoma of the head and neck ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND B-cell chronic lymphocytic leukemia ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Brainstem glioma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Ovarian serous cystadenocarcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Myelodysplastic syndrome ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Prostate adenocarcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Breast neoplasm ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Carcinoma of esophagus ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Gastric adenocarcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Multiple myeloma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Uterine carcinosarcoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Neoplasm of brain ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Squamous cell lung carcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Hepatocellular carcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Transitional cell carcinoma of the bladder ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Neoplasm ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Neoplasm of the large intestine ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Medulloblastoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Malignant neoplasm of body of uterus ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Squamous cell carcinoma of the skin ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Malignant melanoma of skin ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Pancreatic adenocarcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND multiple conditions ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND multiple conditions ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND multiple conditions ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Neoplasm of ovary ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Lip and oral cavity carcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Choroid plexus carcinoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Gallbladder cancer ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Congenital fibrosarcoma ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Breast and/or ovarian cancer ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Gastric cancer ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Malignant lymphoma, large B-cell, diffuse ClinVar Detail
NM_000546.6(TP53):c.742C>T (p.Arg248Trp) AND Adrenocortical carcinoma, hereditary ClinVar Detail
Mutant p53 R248Q but not R248W enhances in vitro invasiveness of human lung cancer NCI-H1299 cells. DisGeNET Detail
NA DisGeNET Detail
Mutant p53 R248Q but not R248W enhances in vitro invasiveness of human lung cancer NCI-H1299 cells. DisGeNET Detail
NA DisGeNET Detail
NA DisGeNET Detail
Using the whole-cell recording mode of the patch-clamp technique, functional ion channels were elect... DisGeNET Detail
Composite adrenal anaplastic neuroblastoma and virilizing adrenocortical tumor with germline TP53 R2... DisGeNET Detail
In matched samples, immunohistochemistry evaluation of p53 protein expression revealed the presence ... DisGeNET Detail
To elucidate whether and how mutant p53 acquires its gain-of-function, mutant p53 is inducibly knock... DisGeNET Detail
Here, we report a family with LFS harboring a germline TP53 mutation (R248W) located in the function... DisGeNET Detail
Using the whole-cell recording mode of the patch-clamp technique, functional ion channels were elect... DisGeNET Detail
We report a patient with composite neuroblastoma (NB), adrenocortical tumor (ACT), and Li-Fraumeni s... DisGeNET Detail
Using short hairpin RNA against p53, transient ectopic expression of wild-type p53 or mutant p53 (R2... DisGeNET Detail
Overexpression of the paradigmatic p53 mutants p53(R175H), p53(R248W) and p53(R273H) in the p53 null... DisGeNET Detail
Using the whole-cell recording mode of the patch-clamp technique, functional ion channels were elect... DisGeNET Detail
Using the whole-cell recording mode of the patch-clamp technique, functional ion channels were elect... DisGeNET Detail
Adoptive overexpression of wild-type p53, but not of its inactive (R248W and R273H) mutants, strongl... DisGeNET Detail
To elucidate whether and how mutant p53 acquires its gain-of-function, mutant p53 is inducibly knock... DisGeNET Detail
Composite adrenal anaplastic neuroblastoma and virilizing adrenocortical tumor with germline TP53 R2... DisGeNET Detail
Composite adrenal anaplastic neuroblastoma and virilizing adrenocortical tumor with germline TP53 R2... DisGeNET Detail

Overlapped Transcript Coordinates

Gene Transcript ID Exon Number Chromosome Start Stop Type Amino Mutation Transcript Position Links

Overlapped Transcript

Gene Transcript ID Chromosome Start Stop Links
Gene
-
dbSNP
rs121912651 dbSNP
Genome
hg38
Position
chr17:7,674,221-7,674,221
Variant Type
snv
Reference Allele
G
Alternative Allele
A
East Asian Chromosome Counts (ExAC)
8652
East Asian Allele Counts (ExAC)
0
East Asian Heterozygous Counts (ExAC)
0
East Asian Homozygous Counts (ExAC)
0
East Asian Allele Frequency (ExAC)
0.0
Chromosome Counts in All Race (ExAC)
121366
Allele Counts in All Race (ExAC)
1
Heterozygous Counts in All Race (ExAC)
1
Homozygous Counts in All Race (ExAC)
0
Allele Frequency in All Race (ExAC)
8.239539904091756E-6
Variant (CIViC) (CIViC Variant)
R248W
Transcript 1 (CIViC Variant)
ENST00000269305.4
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/118
Summary (CIViC Variant)
While loss-of-function events in TP53 are very common in cancer, the R248 variants seem not only to result in loss of tumor-suppression, but also act as a gain-of-function mutation that can promote tumorigenesis in mouse models. This mutant is also more responsive to treatment with doxorubicin than its wild-type counterparts. While the prognostic impact of individual TP53 mutations is influenced by the cohort being studied, R248 mutations have been shown to confer worse overall survival.
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