ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.596G>T (p.Gly199Val) (rs1555525857)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522967 SCV000620549 likely pathogenic not provided 2018-06-20 criteria provided, single submitter clinical testing This apparently mosaic variant is denoted TP53 c.596G>T at the cDNA level, p.Gly199Val (G199V) atthe protein level, and results in the change of a Glycine to a Valine (GGA>GTA). This variant has not been reported ina peer-reviewed publication as a germline observation, but it is present in the International Agency for Research onCancer (IARC) TP53 database, reported in the germline of a patient with a sarcoma and a family history ofadrenocortical carcinoma and breast cancer (IARC). Functional assays show this variant is unable to transactivatetarget genes and gains anti-apoptotic function in a cancer cell line (Kim 2009, Ji 2014). In addition, this variant isreported as having non-functional transactivation in the IARC TP53 database based on functional assays by Kato et al.(2003). TP53 Gly199Val was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000Genomes Consortium 2015, Lek 2016). Since Glycine and Valine share similar properties, this is considered aconservative amino acid substitution. TP53 Gly199Val occurs at a position that is conserved across species and islocated in the DNA binding domain (Bode 2004). In silico analyses predict that this variant is probably damaging toprotein structure and function. Based on the currently available evidence, we consider TP53 Gly199Val to be a likelypathogenic variant.

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