ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.821T>G (rs1057520006)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492506 SCV000581158 likely pathogenic Hereditary cancer-predisposing syndrome 2017-10-03 criteria provided, single submitter clinical testing The p.V274G variant (also known as c.821T>G), located in coding exon 7 of the TP53 gene, results from a T to G substitution at nucleotide position 821. The valine at codon 274 is replaced by glycine, an amino acid with dissimilar properties. This alteration has been reported in the IARC TP53 data base as a somatic alteration in 10 tumors, however it has not been reported as a germline alteration (Petitjean A et al. IARC TP53 database [version R16, November 2012]. Hum Mutat. 2007 Jun;28(6):622-9). This alteration is located in the DNA binding domain, and has shown temperature sensitivity and loss of transactivation capacity in yeast based functional assays (Kato S et al. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9; Grochova D et al. Oncogene 2008 Feb; 27(9):1243-52). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Cho Y, Science 1994 Jul; 265(5170):346-55). This amino acid position is not well conserved in available vertebrate species. However, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV000692432 SCV000820257 uncertain significance Li-Fraumeni syndrome 2020-05-25 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 274 of the TP53 protein (p.Val274Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 376676). Experimental studies in yeast and mammalian cells have shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609, 17724467, 20505364). 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.
Database of Curated Mutations (DoCM) RCV000426446 SCV000510024 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437117 SCV000510025 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419865 SCV000510026 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430539 SCV000510027 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441279 SCV000510028 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420544 SCV000510029 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431168 SCV000510030 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438367 SCV000510031 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421122 SCV000510032 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431803 SCV000510033 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439046 SCV000510034 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Institute of Medical Sciences, Banaras Hindu University RCV001255678 SCV001432243 pathogenic Lip and oral cavity carcinoma 2019-04-30 no assertion criteria provided research

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