ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.722C>G (p.Ser241Cys) (rs28934573)

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Total submissions: 23
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492778 SCV000581139 likely pathogenic Hereditary cancer-predisposing syndrome 2016-02-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting pathogenic classification,Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Database of Curated Mutations (DoCM) RCV000431373 SCV000509724 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442616 SCV000509725 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425780 SCV000509726 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432564 SCV000509727 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442642 SCV000509728 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426900 SCV000509729 likely pathogenic Papillary renal cell carcinoma, sporadic 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437089 SCV000509730 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419417 SCV000509731 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426195 SCV000509732 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438178 SCV000509733 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420364 SCV000509734 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430604 SCV000509735 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439098 SCV000509736 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417965 SCV000509737 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428236 SCV000509738 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438488 SCV000509739 likely pathogenic Non-Hodgkin lymphoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422573 SCV000509740 likely pathogenic Carcinoma of gallbladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429339 SCV000509741 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439590 SCV000509742 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
GeneDx RCV000236210 SCV000293500 likely pathogenic not provided 2018-04-10 criteria provided, single submitter clinical testing This variant is denoted TP53 c.722C>G at the cDNA level, p.Ser241Cys (S241C) at the protein level, and results in the change of a Serine to a Cysteine (TCC>TGC). This variant has not, to our knowledge, been reported as a germline variant; however it has been reported as a somatic variant in multiple different tumor types (Laframboise 2000, Powell 2000, Koul 2002, Jordan 2010, COSMIC). This variant 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 also demonstrated loss of transactivation capacity in a yeast functional assay (Jordan 2010). TP53 Ser241Cys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. TP53 Ser241Cys occurs at a position that is conserved across species and is located in the DNA binding domain and the region of interaction with CCAR2, HIPK1, and AXIN1 (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available evidence, we consider TP53 Ser241Cys to be a likely pathogenic variant.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785321 SCV000923889 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154419 SCV000204087 likely pathogenic Li-Fraumeni syndrome 2008-01-03 no assertion criteria provided clinical testing

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