ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.724T>G (p.Cys242Gly) (rs1057519982)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461418 SCV000545262 uncertain significance Li-Fraumeni syndrome 2016-09-05 criteria provided, single submitter clinical testing This sequence change replaces cysteine with glycine at codon 242 of the TP53 protein (p.Cys242Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TP53-related disease. A different missense substitution at this codon (p.Cys242Tyr) has been determined to be pathogenic (Invitae databse). This suggests that the cysteine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. An experimental study has shown that this missense change significantly reduces the transcriptional transactivation activity of the TP53 protein in yeast-based assays (PMID: 12826609). In summary, this variant is a novel missense change that has been shown to disrupt protein function in vitro, and a different missense change at this residue has been classified as pathogenic. However, without additional functional and/or genetic data, it has been classified as a Variant of Uncertain Significance.
Database of Curated Mutations (DoCM) RCV000442190 SCV000507813 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426704 SCV000507814 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437385 SCV000507815 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444807 SCV000507816 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427357 SCV000507817 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438030 SCV000507818 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420803 SCV000507819 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428013 SCV000507820 likely pathogenic Chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435223 SCV000507821 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417900 SCV000507822 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428578 SCV000507823 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only

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