ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.730G>A (p.Gly244Ser) (rs1057519989)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492366 SCV000581152 likely pathogenic Hereditary cancer-predisposing syndrome 2017-07-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Deficient protein function in appropriate functional assay(s),Structural Evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Good segregation with disease (lod 1.5-3 = 5-9 meioses)
Database of Curated Mutations (DoCM) RCV000421362 SCV000508160 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432031 SCV000508161 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441006 SCV000508162 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423748 SCV000508163 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434459 SCV000508164 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443654 SCV000508165 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426513 SCV000508166 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433704 SCV000508167 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442909 SCV000508168 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425382 SCV000508169 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436060 SCV000508170 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418805 SCV000508171 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426057 SCV000508172 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Invitae RCV000633372 SCV000754594 pathogenic Li-Fraumeni syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 244 of the TP53 protein (p.Gly244Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature to segregate with Li-Fraumeni syndrome and breast cancer in families (PMID: 18511570, 26818906, 25925845) and has also been found in individuals affected with primary ciliary dyskinesia and follicular lymphoma (PMID: 18628487, 24307375). ClinVar contains an entry for this variant (Variation ID: 376600). Experimental studies have shown that this missense change disrupts the transcriptional transactivation function of the TP53 protein (PMID: 12826609). A different missense substitution at this codon (p.Gly244Asp) has been determined to be pathogenic (PMID: 16494995, 21343334, 22319594). This suggests that the glycine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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