ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.701A>C (p.Tyr234Ser) (rs587780073)

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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 RCV001025931 SCV001188214 likely pathogenic Hereditary cancer-predisposing syndrome 2019-08-07 criteria provided, single submitter clinical testing The p.Y234S variant (also known as c.701A>C), located in coding exon 6 of the TP53 gene, results from an A to C substitution at nucleotide position 701. The tyrosine at codon 234 is replaced by serine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation in yeast based assays (IARC TP53 database: 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 (Kotler E et al. Mol. Cell 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). Additionally, two other substitutions at this same amino acid position, p.Y234D and p.Y234H, have been reported in individuals with a personal history that is consistent with TP53-associated disease<span style="font-family:calibri; font-size:11.0pt"> (Mitchell G et al. PLoS ONE 2013 ; 8(7):e69026; Ambry internal data). 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.
Invitae RCV001341542 SCV001535421 uncertain significance Li-Fraumeni syndrome 2020-06-14 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with serine at codon 234 of the TP53 protein (p.Tyr234Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. 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: 376690). This variant has been reported to affect TP53 protein function (PMID: 12826609, 29979965, 30224644, 30840781). This variant disrupts the p.Tyr234 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12695689, 28724667, 26556299, 23894400, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) RCV000430039 SCV000510299 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440245 SCV000510300 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423467 SCV000510301 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430207 SCV000510302 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439556 SCV000510303 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421924 SCV000510304 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433051 SCV000510305 likely pathogenic Adrenocortical carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444569 SCV000510306 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421263 SCV000510307 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431511 SCV000510308 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444596 SCV000510309 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427293 SCV000510310 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437540 SCV000510311 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443862 SCV000510312 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only

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