ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.66A>G (p.Leu22=) (rs748527030)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163369 SCV000213908 likely benign Hereditary cancer-predisposing syndrome 2014-08-08 criteria provided, single submitter clinical testing
Color RCV000163369 SCV000686760 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-19 criteria provided, single submitter clinical testing
GeneDx RCV000483133 SCV000565620 uncertain significance not provided 2018-05-24 criteria provided, single submitter clinical testing This variant is denoted TP53 c.66A>G at the DNA level. This variant is silent at the coding level, preserving a Leucine at codon 22. Although this variant is not predicted to affect splicing, it is located at a position that potentially impacts the tertiary structure of p53 mRNA (F?hraeus 2015). This variant was observed in various assays to reduce several functions including p53-induced apoptosis, p53 mRNA binding to MDM2, in vitro transcription and internal ribosome entry site activity (Candeias 2008, Grover 2011, Malbert-Colas 2014). TP53 c.66A>G was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether TP53 c.66A>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000196762 SCV000254635 likely benign Li-Fraumeni syndrome 2017-01-23 criteria provided, single submitter clinical testing
Mendelics RCV000196762 SCV000839128 uncertain significance Li-Fraumeni syndrome 2018-07-02 criteria provided, single submitter clinical testing

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