ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.832C>A (p.Pro278Thr)

dbSNP: rs17849781
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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002429348 SCV002680528 pathogenic Hereditary cancer-predisposing syndrome 2020-09-30 criteria provided, single submitter clinical testing The p.P278T pathogenic mutation (also known as c.832C>A), located in coding exon 7 of the TP53 gene, results from a C to A substitution at nucleotide position 832. The proline at codon 278 is replaced by threonine, an amino acid with highly similar properties. This alteration was identified in one family reported to meet LFS criteria (Güran S et al. Cancer Genet. Cytogenet., 2005 Jul;160:164-8). This variant is in the DNA binding domain of the TP53 protein and is reported to have non-functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect ([Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8;] Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This alteration has been observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Invitae RCV002524698 SCV003443708 pathogenic Li-Fraumeni syndrome 2023-08-11 criteria provided, single submitter clinical testing Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). This variant disrupts the p.Pro278 amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in individuals with TP53-related conditions (PMID: 8688334, 11370630; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 376643). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 278 of the TP53 protein (p.Pro278Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 15993273).
Myriad Genetics, Inc. RCV004022234 SCV004931143 likely pathogenic Li-Fraumeni syndrome 1 2024-02-20 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].
Database of Curated Mutations (DoCM) RCV000433992 SCV000509060 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442861 SCV000509061 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425201 SCV000509062 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435065 SCV000509063 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442983 SCV000509064 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425878 SCV000509065 likely pathogenic Ovarian serous cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436548 SCV000509066 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418460 SCV000509067 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429149 SCV000509068 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437214 SCV000509069 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419944 SCV000509070 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429755 SCV000509071 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440415 SCV000509072 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Oxford Haemato-Oncology Service, Oxford University Hospitals NHS Foundation Trust RCV000626445 SCV000734835 drug response Poly (ADP-Ribose) polymerase inhibitor response 2017-11-27 no assertion criteria provided clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne RCV000785511 SCV000924083 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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