ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.730G>T (p.Gly244Cys) (rs1057519989)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538079 SCV000629861 uncertain significance Li-Fraumeni syndrome 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 244 of the TP53 protein (p.Gly244Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 376599). An experimental study in yeast has shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609) Two different missense substitutions at this codon (p.Gly244Asp and p.Gly244Ser) have been determined to be pathogenic (PMID: 16494995, 21343334, 22319594, 26818906, 25925845). This suggests that the glycine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a rare missense change at the important residue that has shown to affect protein function. In the absence of additional data, this variant has been classified as a Variant of Uncertain Significance.
Institute of Biochemistry, Molecular Biology and Biotechnology,University of Colombo RCV001270273 SCV001450490 pathogenic Familial cancer of breast criteria provided, single submitter case-control
GeneDx RCV001567979 SCV001791762 pathogenic not provided 2019-12-30 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: non-functional transactivation and loss of growth suppression ability (Kato 2003, Kotler 2018); Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31711486, 30123427, 31186738, 31588418, 29979965, 10226610, 20557307, 22931248, 22551440, 15580553, 11307149, 15902285, 14722922, 19558493, 31168460)
Database of Curated Mutations (DoCM) RCV000437805 SCV000508147 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443459 SCV000508148 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427774 SCV000508149 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436692 SCV000508150 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419449 SCV000508151 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430162 SCV000508152 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437360 SCV000508153 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418385 SCV000508154 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429067 SCV000508155 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439724 SCV000508156 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422508 SCV000508157 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427875 SCV000508158 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438569 SCV000508159 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only

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