ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.746G>A (p.Arg249Lys) (rs587782329)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131246 SCV000186204 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724753 SCV000232077 uncertain significance not provided 2015-04-22 criteria provided, single submitter clinical testing
GeneDx RCV000724753 SCV000567602 uncertain significance not provided 2015-08-06 criteria provided, single submitter clinical testing This variant is denoted TP53 c.746G>A at the cDNA level, p.Arg249Lys (R249K) at the protein level, and results in the change of an Arginine to a Lysine (AGG>AAG). This variant has not, to our knowledge, been published in the literature as a germline variant; however, TP53 Arg249Lys has been reported as a somatic variant in multiple different tumor types (Cosmic, IARC TP53 Database). TP53 Arg249Lys has also been reported as having non-functional transactivation activity in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003) and demonstrated reduced transcriptional activity in a yeast functional assay (Van der Vorst 2012). TP53 Arg249Lys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Arginine and Lysine share similar properties, this is considered a conservative amino acid substitution. TP53 Arg249Lys occurs at a position that is conserved across species and is located in the region of interaction with CCAR2, HIPK1, and ZNF385A (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether TP53 Arg249Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Database of Curated Mutations (DoCM) RCV000420497 SCV000509419 likely pathogenic Medulloblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427275 SCV000509420 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437502 SCV000509421 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419850 SCV000509422 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430131 SCV000509423 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440358 SCV000509424 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419499 SCV000509425 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429319 SCV000509426 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439985 SCV000509427 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421887 SCV000509428 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429077 SCV000509429 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438874 SCV000509430 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421647 SCV000509431 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431473 SCV000509432 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445113 SCV000509433 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only

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