ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.423C>G (p.Cys141Trp) (rs1057519977)

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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 RCV000492201 SCV000581134 likely pathogenic Hereditary cancer-predisposing syndrome 2016-12-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting pathogenic classification
Database of Curated Mutations (DoCM) RCV000430241 SCV000507534 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440499 SCV000507535 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422816 SCV000507536 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434797 SCV000507537 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442353 SCV000507538 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423924 SCV000507539 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434169 SCV000507540 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444942 SCV000507541 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424802 SCV000507542 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431589 SCV000507543 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445034 SCV000507544 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425931 SCV000507545 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Invitae RCV000467641 SCV000545329 uncertain significance Li-Fraumeni syndrome 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 141 of the TP53 protein (p.Cys141Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with childhood osteosarcoma (PMID: 29946497). ClinVar contains an entry for this variant (Variation ID: 376564). Experimental studies in yeast have shown that this missense change results in compromised TP53 transactivation activity (PMID: 12826609, 20407015). This variant disrupts the p.Cys141Tyr amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 12826609, 10589545, 11370630), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.

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