ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.734G>A (p.Gly245Asp) (rs121912656)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164465 SCV000215109 pathogenic Hereditary cancer-predisposing syndrome 2017-02-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),Well-characterized mutation at same position,Other strong data supporting pathogenic classification,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Database of Curated Mutations (DoCM) RCV000440814 SCV000508199 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421831 SCV000508200 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429017 SCV000508201 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439739 SCV000508202 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422520 SCV000508203 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431450 SCV000508204 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444212 SCV000508205 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421349 SCV000508206 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432021 SCV000508207 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444304 SCV000508208 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427250 SCV000508209 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437916 SCV000508210 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443515 SCV000508211 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426192 SCV000508212 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436871 SCV000508213 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419718 SCV000508214 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785472 SCV000924044 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000206683 SCV000261202 pathogenic Li-Fraumeni syndrome 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 245 of the TP53 protein (p.Gly245Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Li Fraumeni syndrome-associated cancers in a single family (PMID: 2259385) and also has been reported in individuals affected with chronic lymphocytic leukemia and chronic-phase primary myelofibrosis (PMID: 21232794, 22052707). ClinVar contains an entry for this variant (Variation ID: 12355). Experimental studies have shown that this missense change severely affects the functional activity of the p53 protein, abolishing its DNA-binding and transcriptional transactivation activities. This variant is classified as a severe deficiency allele with possible dominant-negative inhibitory effects (PMID: 17606709, 20128691, 12826609, 25119136). In addition, a different missense substitution at this codon (p.Gly245Ser) has been determined to be pathogenic (PMID: 12826609, 12885464, 7783166, 1565143, 1591732, 23538418). 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.
OMIM RCV000013149 SCV000033396 pathogenic Li-Fraumeni syndrome 1 1990-12-20 no assertion criteria provided literature only

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