ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.422G>A (p.Cys141Tyr) (rs587781288)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128975 SCV000172861 pathogenic Hereditary cancer-predisposing syndrome 2016-12-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s)
Database of Curated Mutations (DoCM) RCV000427674 SCV000507522 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437920 SCV000507523 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444430 SCV000507524 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427068 SCV000507525 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435449 SCV000507526 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417795 SCV000507527 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428004 SCV000507528 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436530 SCV000507529 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418811 SCV000507530 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429076 SCV000507531 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439333 SCV000507532 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423419 SCV000507533 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785510 SCV000924082 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000472876 SCV000545264 pathogenic Li-Fraumeni syndrome 2018-11-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 141 of the TP53 protein (p.Cys141Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (rs587781288, ExAC no frequency). This variant has been reported in individuals affected with Li-Fraumeni syndrome (LFS) related cancers (liposarcoma, astrocytoma, Hodgkin lymphoma) in families with a strong history of LFS-related cancers (PMID: 10589545, 11370630, Invitae). It has also been observed in individuals with breast cancer (PMID: 20522432) and chronic lymphocytic leukemia (PMID: 21232794). ClinVar contains an entry for this variant (Variation ID: 140801). Experimental studies have shown that this missense change disrupts the DNA-binding activity (PMID: 20128691) and transcriptional transactivation activity (PMID: 12826609, 16861262, 21343334, 24256616) of the TP53 protein. For these reasons, this variant has been classified as Pathogenic.

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