Total submissions: 20
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000824609 | SCV000965512 | pathogenic | Li-Fraumeni syndrome | 2019-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 281 of the TP53 protein (p.Asp281Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs764146326, ExAC 0.01%). This variant has been observed in an individual with osteosarcoma (PMID: 23894400) and has been observed to be de novo in an individual affected with early-onset bilateral breast cancer (PMID: 17572079). ClinVar contains an entry for this variant (Variation ID: 376586). Experimental studies have shown that this variant impairs the transcriptional transactivation activity of the TP53 protein and can act as a dominant negative allele (PMID: 12826609, 11896595, 19850740). This variant disrupts the p.Asp281 amino acid residue in TP53. Other variants that disrupt this residue have been determined to be pathogenic (PMID: 15925506, 25293557, 10864200, 12826609; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Database of Curated Mutations |
RCV000429505 | SCV000507906 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439749 | SCV000507907 | likely pathogenic | Renal cell carcinoma, papillary, 1 | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422096 | SCV000507908 | likely pathogenic | Neuroblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428837 | SCV000507909 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438896 | SCV000507910 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421233 | SCV000507911 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431489 | SCV000507912 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443405 | SCV000507913 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424002 | SCV000507914 | likely pathogenic | Chronic lymphocytic leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434267 | SCV000507915 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443489 | SCV000507916 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426863 | SCV000507917 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437075 | SCV000507918 | likely pathogenic | Uterine Carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442054 | SCV000507919 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426180 | SCV000507920 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436424 | SCV000507921 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418705 | SCV000507922 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428968 | SCV000507923 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne, |
RCV000785452 | SCV000924024 | likely pathogenic | Neoplasm of ovary | 2018-12-01 | no assertion criteria provided | research |