ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.556G>A (p.Asp186Asn) (rs1060501206)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467183 SCV000545352 uncertain significance Li-Fraumeni syndrome 2016-06-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 186 of the TP53 protein (p.Asp186Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with chronic lymphocytic leukemia (PMID: 21232794). Experimental studies have shown that this missense change does not affect the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). In summary, this variant is a rare missense change that does not affect the transcriptional transactivation activity of the TP53 protein although the effect of this change on other aspects of protein function has not been established. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000481372 SCV000566478 uncertain significance not provided 2015-05-03 criteria provided, single submitter clinical testing This variant is denoted TP53 c.556G>A at the cDNA level, p.Asp186Asn (D186N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). This variant has not, to our knowledge, been published in the literature as a germline pathogenic variant in humans, but has been reported in association with multiple tumor types including ovarian (confirmed somatic), chronic lymphocytic leukemia, upper airway and urinary tract (COSMIC, Pekova 2011). TP53 Asp186Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Aspartic Acid and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution. TP53 Asp186Asn occurs at a position that is conserved in mammals and is located within the regions of interaction with HIPK1, ZNF385A, FBXO42 and AXIN1 (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether TP53 Asp186Asn is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000571882 SCV000664581 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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.