ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.907A>G (p.Ser303Gly) (rs587782391)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen TP53 Variant Curation Expert Panel,ClinGen RCV001527095 SCV001737938 likely benign Li-Fraumeni syndrome 1 2021-05-07 reviewed by expert panel curation This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). Transactivation assays show supertransactivation function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). In summary, TP53 c.907A>G (p.Ser303Gly) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BP4, PM2_Supporting.
Ambry Genetics RCV000131400 SCV000186376 likely benign Hereditary cancer-predisposing syndrome 2020-07-07 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
Invitae RCV000549010 SCV000629885 uncertain significance Li-Fraumeni syndrome 2020-05-25 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 303 of the TP53 protein (p.Ser303Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 142332). Experimental studies have shown that this variant outperforms the transactivation activity of the TP53 protein function over the wild-type in yeast-based assays (PMID: 12826609). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760105 SCV000889887 uncertain significance not provided 2018-03-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131400 SCV000908782 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-16 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.