ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.833C>A (p.Pro278His) (rs876659802)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633329 SCV000754551 uncertain significance Li-Fraumeni syndrome 2019-04-24 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 278 of the TP53 protein (p.Pro278His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. 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 hereditary cancer. ClinVar contains an entry for this variant (Variation ID: 376646). Experimental studies in yeast have shown that this variant impairs TP53 protein transcriptional activity (PMID: 12826609, 16861262). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001017582 SCV001178679 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-11 criteria provided, single submitter clinical testing The p.P278H variant (also known as c.833C>A), located in coding exon 7 of the TP53 gene, results from a C to A substitution at nucleotide position 833. The proline at codon 278 is replaced by histidine, an amino acid with similar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation capacity in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. U.S.A. 2003 Jul 8;100(14):8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression (Kotler E et al. Mol. Cell 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Database of Curated Mutations (DoCM) RCV000422133 SCV000509099 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433712 SCV000509100 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444453 SCV000509101 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426301 SCV000509102 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433513 SCV000509103 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443564 SCV000509104 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427682 SCV000509105 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437485 SCV000509106 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420265 SCV000509107 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424797 SCV000509108 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435517 SCV000509109 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417607 SCV000509110 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428293 SCV000509111 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only

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