ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.537T>G (p.His179Gln) (rs876660821)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000815181 SCV000955628 pathogenic Li-Fraumeni syndrome 2019-11-12 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 179 of the TP53 protein (p.His179Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast cancer or acute myeloid leukemia (PMID: 28724667, 26230955). ClinVar contains an entry for this variant (Variation ID: 376607). Experimental studies have shown that this missense change results in defective TP53 transactivation activity and severely attenuated cell-cycle checkpoint function (PMID: 12826609, 17311302, 16209708, 22540896). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. A different variant (c.537T>A) giving rise to the same protein effect observed here (p.His179Gln) has been determined to be pathogenic (PMID: 19556618). This suggests that this variant is also likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Database of Curated Mutations (DoCM) RCV000444951 SCV000508371 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421558 SCV000508372 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431364 SCV000508373 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444976 SCV000508374 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425896 SCV000508375 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436580 SCV000508376 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444017 SCV000508377 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425641 SCV000508378 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437195 SCV000508379 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419975 SCV000508380 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429821 SCV000508381 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436952 SCV000508382 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420594 SCV000508383 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431267 SCV000508384 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441082 SCV000508385 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423857 SCV000508386 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428479 SCV000508387 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439103 SCV000508388 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421045 SCV000508389 likely pathogenic Carcinoma of gallbladder 2016-05-31 no assertion criteria provided literature only

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