ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.820G>T (p.Val274Phe)

dbSNP: rs1057520005
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001344689 SCV001538756 uncertain significance Li-Fraumeni syndrome 2020-07-09 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 274 of the TP53 protein (p.Val274Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 376674). This variant has been reported to affect TP53 protein function (PMID: 12826609, 16741917, 27911860, 11920959, 30224644). 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.
Ambry Genetics RCV002429349 SCV002679731 pathogenic Hereditary cancer-predisposing syndrome 2021-11-19 criteria provided, single submitter clinical testing The p.V274F pathogenic mutation (also known as c.820G>T), located in coding exon 7 of the TP53 gene, results from a G to T substitution at nucleotide position 820. The valine at codon 274 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration has been observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). This variant is in the DNA binding domain of the TP53 protein and is reported to have non-functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8;Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV004022248 SCV004932760 likely pathogenic Li-Fraumeni syndrome 1 2024-02-20 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 12782597, 11920959, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].
Database of Curated Mutations (DoCM) RCV000435470 SCV000510002 likely pathogenic Prostate adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418237 SCV000510003 likely pathogenic Ovarian serous cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428932 SCV000510004 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436116 SCV000510005 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418736 SCV000510006 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429450 SCV000510007 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440120 SCV000510008 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419355 SCV000510009 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430114 SCV000510010 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440773 SCV000510011 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423526 SCV000510012 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Institute of Medical Sciences, Banaras Hindu University RCV001255677 SCV001432242 pathogenic Lip and oral cavity carcinoma 2019-04-30 no assertion criteria provided research

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