ClinVar Miner

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

dbSNP: rs535274413
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Total submissions: 4
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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
Labcorp Genetics (formerly Invitae), Labcorp RCV000791760 SCV000931022 likely benign Li-Fraumeni syndrome 2023-03-28 criteria provided, single submitter clinical testing

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