ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.28G>C (p.Val10Leu)

dbSNP: rs535274413
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen TP53 Variant Curation Expert Panel, ClinGen RCV001723807 SCV001949923 likely benign Li-Fraumeni syndrome 1 2021-08-02 reviewed by expert panel curation 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). . This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). This variant has been observed in 4 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributors). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org) In summary, NM_000546.5(TP53):c.28G>C (p.Val10Leu) 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, PM2_Supporting, BP4, BS2_Supporting.
Ambry Genetics RCV000220427 SCV000275220 likely benign Hereditary cancer-predisposing syndrome 2020-03-23 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000220427 SCV000904841 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-13 criteria provided, single submitter clinical testing
Invitae RCV000791760 SCV000931022 likely benign Li-Fraumeni syndrome 2023-03-28 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.