ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.518T>A (p.Val173Glu) (rs1057519747)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574130 SCV000667212 likely pathogenic Hereditary cancer-predisposing syndrome 2017-10-09 criteria provided, single submitter clinical testing The p.V173E variant (also known as c.518T>A), located in coding exon 4 of the TP53 gene, results from a T to A substitution at nucleotide position 518. The valine at codon 173 is replaced by glutamic acid, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to exhibit loss of transactivation capacity in vitro and predicted to affect several p53 isoforms (IARC TP53 database; Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). Further, a similar alteration, p.V173M (c.517G>A), has been reported in a family meeting clinical criteria for Li-Fraumeni Syndrome (Achatz M et al. Cancer Lett. 2007 Jan; 245(1-2):96-102). Alterations at codon 173 have been reported in the literature in multiple tumor types including, but not limited to, bronchogenic carcinoma, multiple myeloma, colorectal carcinoma, astrocytic tumors, chronic lymphocytic leukemia (CLL) and oral squamous cell carcinoma (Filip AA et al. Ann. Hematol., 2017 Jan;96:33-50; Flaman JM et al. Proc. Natl. Acad. Sci. U.S.A., 1995 Apr;92:3963-7; Gorgoulis VG et al. Br. J. Cancer, 1998;77:374-84; Groenendijk FH et al. J. Neurooncol., 2011 Feb;101:405-17; Hassan NM et al. Cancer Lett., 2008 Oct;270:108-19; Kortüm KM et al. Blood, 2016 Sep;128:1226-33; Leuci V et al. J Transl Med, 2016 May;14:119). This amino acid position is well 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.
Database of Curated Mutations (DoCM) RCV000443122 SCV000509891 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421130 SCV000509892 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431387 SCV000509893 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443047 SCV000509894 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425654 SCV000509895 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435883 SCV000509896 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442089 SCV000509897 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425882 SCV000509898 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437016 SCV000509899 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419351 SCV000509900 likely pathogenic Adrenocortical carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430481 SCV000509901 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437139 SCV000509902 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420346 SCV000509903 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430605 SCV000509904 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441782 SCV000509905 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Mayo Clinic Laboratories, Mayo Clinic RCV000582350 SCV000692084 uncertain significance not specified no assertion criteria provided clinical testing

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