ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.536A>C (p.His179Pro) (rs1057519991)

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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 RCV001023982 SCV001185931 likely pathogenic Hereditary cancer-predisposing syndrome 2019-03-19 criteria provided, single submitter clinical testing The p.H179P variant (also known as c.536A>C), located in coding exon 4 of the TP53 gene, results from an A to C substitution at nucleotide position 536. The histidine at codon 179 is replaced by proline, an amino acid with similar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have partial loss of transactivation capacity (IARC TP53 database; 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 (Kotler E et al. Mol.Cell, 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet., 2018 Oct;50:1381-1387). The amino acid residue altered by this variant has been shown to be functionally important for zinc binding, and alterations affecting this amino acid have been associated with poorer prognosis in breast cancer patients (Martin AC et al. Hum. Mutat., 2002 Feb;19:149-64; Olivier M et al. Clin. Cancer Res., 2006 Feb;12:1157-67). In addition, other alterations at this same position, p.H179Q (c.537T>A) and p.H179Q (c.537T>G), have been identified as de novo and/or in patients with features suggestive of Li-Fraumeni or Li-Fraumeni-like syndrome (Bougeard G et al. J Med Genet. 2008 Aug;45(8):535-8; Gonzalez KD et al. J. Med. Genet. 2009 Oct; 46(10):689-93). 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 majority of available evidence to date, this variant is likely to be pathogenic.
Database of Curated Mutations (DoCM) RCV000431234 SCV000508447 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441519 SCV000508448 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421224 SCV000508449 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427925 SCV000508450 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439058 SCV000508451 likely pathogenic Carcinoma of gallbladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421433 SCV000508452 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432547 SCV000508453 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444604 SCV000508454 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422328 SCV000508455 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433456 SCV000508456 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444694 SCV000508457 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426919 SCV000508458 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437164 SCV000508459 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443703 SCV000508460 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427172 SCV000508461 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438275 SCV000508462 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420510 SCV000508463 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428125 SCV000508464 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434884 SCV000508465 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only

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