ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.535C>G (p.His179Asp)

dbSNP: rs587780070
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 24
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001851020 SCV002230464 pathogenic Li-Fraumeni syndrome 2023-08-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His179 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11896595, 12509279, 12726864, 12826609, 16633321, 17530187, 18511570, 25433984, 26497680). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). 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. ClinVar contains an entry for this variant (Variation ID: 376610). This missense change has been observed in individuals with clinical features of Li-Fraumeni syndrome (PMID: 32658383; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 179 of the TP53 protein (p.His179Asp).
Ambry Genetics RCV002348144 SCV002645091 likely pathogenic Hereditary cancer-predisposing syndrome 2023-08-02 criteria provided, single submitter clinical testing The p.H179D variant (also known as c.535C>G), located in coding exon 4 of the TP53 gene, results from a C to G substitution at nucleotide position 535. The histidine at codon 179 is replaced by aspartic acid, an amino acid with similar properties. This alteration has been reported as a de novo alteration in a male with no tumor history from a cohort of known TP53 mutation carriers (Renaux-Petel M et al. J. Med. Genet., 2018 03;55:173-180). This alteration has also been reported in a patient with a personal history of rhabdomyosarcoma of embryonal anaplastic subtype diagnosed at age 3 (Pondrom M et al. Pediatr Blood Cancer, 2020 Sep;67:e28486). This variant is in the DNA binding domain of the TP53 protein and is reported to have partial loss of transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Additional 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). 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; Sheng S et al. Int. J. Cancer, 2020 01;146:487-495). This amino acid position is highly conserved in available vertebrate species. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002465649 SCV002760884 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003335320 SCV004045022 pathogenic Li-Fraumeni syndrome 1 2023-06-13 criteria provided, single submitter clinical testing This variant is considered pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 21590121, 29070607, 32658383].
Baylor Genetics RCV003470376 SCV004206262 likely pathogenic Adrenocortical carcinoma, hereditary 2024-01-23 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000440707 SCV000508428 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423899 SCV000508429 likely pathogenic Ovarian serous cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430612 SCV000508430 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441771 SCV000508431 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424030 SCV000508432 likely pathogenic Uterine carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431709 SCV000508433 likely pathogenic Gallbladder carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444992 SCV000508434 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421694 SCV000508435 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431956 SCV000508436 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444860 SCV000508437 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425288 SCV000508438 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436443 SCV000508439 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443866 SCV000508440 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426383 SCV000508441 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436622 SCV000508442 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419821 SCV000508443 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430072 SCV000508444 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437679 SCV000508445 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420116 SCV000508446 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.