Total submissions: 20
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 |
RCV000417671 | SCV000507942 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424389 | SCV000507943 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438151 | SCV000507944 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420516 | SCV000507945 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430695 | SCV000507946 | likely pathogenic | Chronic lymphocytic leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440974 | SCV000507947 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419836 | SCV000507948 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430093 | SCV000507949 | likely pathogenic | Neuroblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440370 | SCV000507950 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422714 | SCV000507951 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432958 | SCV000507952 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439711 | SCV000507953 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422083 | SCV000507954 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432322 | SCV000507955 | likely pathogenic | Renal cell carcinoma, papillary, 1 | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
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 |
RCV000424902 | SCV000507957 | likely pathogenic | Uterine Carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431703 | SCV000507958 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
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, |
RCV000785286 | SCV000923854 | likely pathogenic | Neoplasm of ovary | 2018-12-01 | no assertion criteria provided | research |