ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.857A>G (p.Glu286Gly) (rs1057519985)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000429960 SCV000508029 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439864 SCV000508030 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419110 SCV000508031 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428935 SCV000508032 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439628 SCV000508033 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421511 SCV000508034 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432174 SCV000508035 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438516 SCV000508036 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421308 SCV000508037 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434654 SCV000508038 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443562 SCV000508039 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427234 SCV000508040 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433559 SCV000508041 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442747 SCV000508042 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426176 SCV000508043 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Invitae RCV000556558 SCV000629880 uncertain significance Li-Fraumeni syndrome 2017-02-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 286 of the TP53 protein (p.Glu286Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature as a germline variant in individuals with a TP53-related disease. Experimental studies have shown that this missense change disrupts TP53 transactivation activity (PMID: 9399658, 11429705, 11896595, 12826609). Additional missense substitutions at this codon (p.Glu286Lys, p.Glu286Ala) have been determined to be pathogenic (PMID: 12826609, 1569604, 17567834, 17606709, 21343334, 25896519). This suggests that the glutamic acid 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 novel missense change that affects an important amino acid residue, but has not been reported in affected individuals. It has been classified as a Variant of Uncertain Significance.

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