ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.809T>C (p.Phe270Ser) (rs1057519986)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481465 SCV000572280 likely pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing This variant is denoted TP53 c.809T>C at the cDNA level, p.Phe270Ser (F270S) at the protein level, and results in the change of a Phenylalanine to a Serine (TTT>TCT). TP53 Phe270Ser has not, to our knowledge, been published as a germline pathogenic or benign variant, however it has been observed as a somatic variant in several different tumor types, including colorectal, endometrial, pancreatic, and breast (Nyiraneza 2011, McConechy 2012, Forbes 2015). This variant is reported as having non-functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003), and also showed defective transactivation and growth suppression in other assays, but no dominant-negative effect (Marutani 1999, Monti 2003, Kotler 2018). TP53 Phe270Ser was not observed in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Bode 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available information, we consider TP53 Phe270Ser to be a likely pathogenic variant.
Invitae RCV000824076 SCV000964957 pathogenic Li-Fraumeni syndrome 2018-09-24 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 270 of the TP53 protein (p.Phe270Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed as de novo in an individual affected with TP53-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 376594). Experimental studies have shown that this missense change reduces the ability of TP53 to transactivate downstream target genes (PMID: 12826609, 12917626). For these reasons, this variant has been classified as Pathogenic.
Database of Curated Mutations (DoCM) RCV000426140 SCV000508089 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437299 SCV000508090 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419602 SCV000508091 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429016 SCV000508092 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439252 SCV000508093 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418965 SCV000508094 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429241 SCV000508095 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438621 SCV000508096 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421032 SCV000508097 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only

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