ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.580C>T (p.Leu194Phe) (rs587780071)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115728 SCV000149637 likely pathogenic not provided 2019-06-21 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect with respect to transcriptional activation, apoptosis, and growth suppression activities (Epstein 1998, Kato 2003, Marzec 2015, Kotler 2018); Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with bilateral breast or lung cancer (Melhem-Bertrandt 2012, Villani 2016); This variant is associated with the following publications: (PMID: 26181206, 18223694, 17070499, 26942128, 25733866, 26378048, 27381050, 26425688, 28580174, 27956623, 26009011, 16443602, 19429664, 12667443, 17344317, 12779080, 7935394, 10884390, 9572492, 28397142, 12826609, 29979965, 21761402, 27501770, 30720243, 30840781)
Invitae RCV001377420 SCV001574751 likely pathogenic Li-Fraumeni syndrome 2020-07-13 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 194 of the TP53 protein (p.Leu194Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 21761402, 27501770, Invitae). ClinVar contains an entry for this variant (Variation ID: 127817). This variant has been reported to affect TP53 protein function (PMID: 9572492, 12826609, 18818522, 29979965, 30224644). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Database of Curated Mutations (DoCM) RCV000419908 SCV000508858 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426684 SCV000508859 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436065 SCV000508860 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418414 SCV000508861 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429595 SCV000508862 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439843 SCV000508863 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417813 SCV000508864 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428029 SCV000508865 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439186 SCV000508866 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421548 SCV000508867 likely pathogenic Neoplasm of uterine cervix 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434383 SCV000508868 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only

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