ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.841G>A (p.Asp281Asn) (rs764146326)

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Total submissions: 20
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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 (DoCM) RCV000429505 SCV000507906 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439749 SCV000507907 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422096 SCV000507908 likely pathogenic Neuroblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428837 SCV000507909 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438896 SCV000507910 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421233 SCV000507911 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431489 SCV000507912 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443405 SCV000507913 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424002 SCV000507914 likely pathogenic Chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434267 SCV000507915 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) 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 (DoCM) RCV000426863 SCV000507917 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437075 SCV000507918 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442054 SCV000507919 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426180 SCV000507920 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436424 SCV000507921 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418705 SCV000507922 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) 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,University Hospital Cologne RCV000785452 SCV000924024 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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