ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.843C>G (p.Asp281Glu) (rs1057519984)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633352 SCV000754574 uncertain significance Li-Fraumeni syndrome 2018-01-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 281 of the TP53 protein (p.Asp281Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). While this variant has been published in the literature (PMID: 24766216, 20407015), it has not been reported in an individual with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376587). A different variant (c.843C>A) giving rise to the same protein effect observed here (p.Asp281Glu) has been reported in an individual affected with osteosarcoma (PMID: 23894400), and in a family affected with Li-Fraumeni syndrome (PMID: 27493922). This variant has been reported in breast and brain tumors (PMID: 20407015, 22844452). Experimental studies have shown that this missense change disrupts the transcriptional transactivation function of the TP53 protein (PMID: 20407015, 12826609). A different missense substitution at this codon (p.Asp281Gly), has been reported to be pathogenic (PMID: 26619011, Invitae).  In addition, other missense substitutions at this codon  (p.Asp281Asn, p.Asp281Tyr, p.Asp281Val, p.Asp281Ala, p.Asp281His) have been reported in individuals with TP53-related cancers (PMID: 17572079, 25293557, 10864200, 17390010, 21305319, 23894400, 15925506). This suggests that the aspartic acid residue may be critical for TP53 protein function. 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) RCV000417671 SCV000507942 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424389 SCV000507943 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438151 SCV000507944 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420516 SCV000507945 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430695 SCV000507946 likely pathogenic Chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440974 SCV000507947 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419836 SCV000507948 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430093 SCV000507949 likely pathogenic Neuroblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440370 SCV000507950 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422714 SCV000507951 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432958 SCV000507952 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439711 SCV000507953 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422083 SCV000507954 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432322 SCV000507955 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443165 SCV000507956 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424902 SCV000507957 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431703 SCV000507958 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443254 SCV000507959 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785286 SCV000923854 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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