ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.370T>A (p.Cys124Ser) (rs730881997)

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
GeneDx RCV000161022 SCV000211741 uncertain significance not provided 2015-11-20 criteria provided, single submitter clinical testing This variant is denoted TP53 c.370T>A at the cDNA level, p.Cys124Ser (C124S) at the protein level, and results in the change of a Cysteine to a Serine (TGC>AGC). This variant has been studied functionally, but with varied results regarding its effect on p53 function (Buzek 2002, Baroni 2004, Stoner 2009, Kim 2010). This variant has also been reported as having functional transactivation activity in the International Agency for Research on Cancer (IARC) TP53 database based on functional assays by Kato et al (2003). TP53 Cys124Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Cysteine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. TP53 Cys124Ser occurs at a position that is conserved in mammals and is located in the DNA binding domain and in a region known to interact with multiple proteins (Uniprot). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether TP53 Cys124Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000574455 SCV000672382 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000574455 SCV000908795 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-16 criteria provided, single submitter clinical testing

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.