ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.814G>T (p.Val272Leu) (rs121912657)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164988 SCV000215682 likely pathogenic Hereditary cancer-predisposing syndrome 2020-05-08 criteria provided, single submitter clinical testing The p.V272L variant (also known as c.814G>T), located in coding exon 7 of the TP53 gene, results from a G to T substitution at nucleotide position 814. The valine at codon 272 is replaced by leucine, an amino acid with highly similar properties. This alteration was first described in a proband with childhood-onset acute lymphoblastic leukemia (ALL) whose personal and family history satisfied diagnostic criteria for classic Li-Fraumeni syndrome (Felix CA J. Clin. Invest. 1992 Feb;89(2):640-7). Functional studies from multiple groups show deficient transactivation capacity and greatly reduced DNA binding activity compared to wild type (Malcikova J Biol. Chem. 391(2-3):197-205. Monti P et al. Mol. Cancer Res. 2011 Mar;9(3):271-9. <span style="font-family:arial,sans-serif; font-size:10pt">IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul 8;100(14):8424-9). This amino acid position is highly conserved through primates, but not in lower 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.
Invitae RCV001221969 SCV001394046 uncertain significance Li-Fraumeni syndrome 2019-04-28 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 272 of the TP53 protein (p.Val272Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with pediatric onset acute lymphoblastic leukemia (PMID: 1737852). ClinVar contains an entry for this variant (Variation ID: 12358). This variant has been reported to affect TP53 protein function (PMID: 12826609, 20128691, 21343334, 28915717, 27533082). 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.
OMIM RCV000013152 SCV000033399 pathogenic Li-Fraumeni syndrome 1 1992-08-01 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432989 SCV000509976 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443570 SCV000509977 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426429 SCV000509978 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437100 SCV000509979 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443589 SCV000509980 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427077 SCV000509981 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437706 SCV000509982 likely pathogenic Medulloblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420507 SCV000509983 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431193 SCV000509984 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434905 SCV000509985 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417682 SCV000509986 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428361 SCV000509987 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439021 SCV000509988 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only

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