ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.712T>C (p.Cys238Arg) (rs1057519981)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492666 SCV000581087 pathogenic Hereditary cancer-predisposing syndrome 2015-07-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),Other strong data supporting pathogenic classification,Well-characterized mutation at same position
Database of Curated Mutations (DoCM) RCV000437018 SCV000507735 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419348 SCV000507736 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430482 SCV000507737 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437199 SCV000507738 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420409 SCV000507739 likely pathogenic Uterine cervical neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430655 SCV000507740 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441834 SCV000507741 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424052 SCV000507742 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428210 SCV000507743 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438447 SCV000507744 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421679 SCV000507745 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431946 SCV000507746 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441879 SCV000507747 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421933 SCV000507748 likely pathogenic Chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433046 SCV000507749 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442237 SCV000507750 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426193 SCV000507751 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Invitae RCV000812726 SCV000953049 pathogenic Li-Fraumeni syndrome 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 238 of the TP53 protein (p.Cys238Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with choroid plexus carcinoma (Invitae). ClinVar contains an entry for this variant (Variation ID: 376576). An experimental study in yeast has shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). This variant disrupts the p.C238 amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID:  12406399, 14673037, 15925506), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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