ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.700T>G (p.Tyr234Asp) (rs864622237)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 16
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204217 SCV000259812 uncertain significance Li-Fraumeni syndrome 2015-08-07 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with aspartic acid at codon 234 of the TP53 protein (p.Tyr234Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. This variant is not present in population databases and has been reported in the literature. This variant was reported in an individual affected with chronic lymphocytic leukemia (PMID: 21232794). It has also been reported in the tumor of a patient with colorectal cancer (PMID: 22982087). Experimental studies in vitro have shown that this missense change may lead to defective transactivation (PMID: 21232794). Other missense mutations, p.Tyr234Cys and p.Tyr234His, have been reported at the same codon in individuals affected with Li-Fraumeni syndrome as well as other isolated cancers (PMID: 12695689, 17606709, 23894400). Experimental studies of these missense mutations suggest that this amino acid may be essential for protein function (PMID: 9290701, 21232794, 21343334). In summary, clinical and experimental evidence suggests that other missense mutations at this position may lead to disrupted protein function. However, evidence directly related this p.Tyr234Asp variant is limited. For these reasons, this change has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000492197 SCV000581114 likely pathogenic Hereditary cancer-predisposing syndrome 2016-03-18 criteria provided, single submitter clinical testing The p.Y234D variant (also known as c.700T>G), located in coding exon 6 of the TP53 gene, results from a T to G substitution at nucleotide position 700. The tyrosine at codon 234 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This variantwas detected in an individual meeting clinical criteria forclassicLi-Fraumenisyndrome(Ambryinternal data).This variant is in the DNA binding domain of theTP53protein and is reported to have loss oftransactivationcapacity and predicted toaffectseveral p53isoforms. (IARCTP53database; Kato S et al.ProcNatlAcadSci USA. 2003 Jul 8;100(14):8424-9).This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position.To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 250000alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. However, based on internal structural analysis, this variant may result in a decrease in structural stability (Cho Y et al.Science1994 Jul; 265(5170):346-55).Additionally, adifferent alterationat the samecodon,p.Y234H, hasbeenreportedin an individual with breast cancer at age 33 and aleiomyosarcomaat age 48,with loss ofheterozygositypresentin the tumor (Mitchell G et al.PLoSONE2013 ; 8(7):e69026).Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Database of Curated Mutations (DoCM) RCV000418073 SCV000510341 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430896 SCV000510342 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441597 SCV000510343 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424345 SCV000510344 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433328 SCV000510345 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440475 SCV000510346 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423238 SCV000510347 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433956 SCV000510348 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445176 SCV000510349 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425587 SCV000510350 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432845 SCV000510351 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445265 SCV000510352 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424462 SCV000510353 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435222 SCV000510354 likely pathogenic Adrenocortical carcinoma 2016-05-31 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.