ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1088G>A (p.Arg363Lys) (rs876660285)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223158 SCV000277582 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000419155 SCV000532945 uncertain significance not provided 2018-12-04 criteria provided, single submitter clinical testing The R363K variant in the TP53 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is reported as having partially functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003). The R363K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R363K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. Missense variants in nearby residues (P359L, H365Y) have been reported in the Human Gene Mutation Database in association with TP53-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the currently available evidence, it is unclear whether this variant is a pathogenic variant or a rare benign variant. We consider it to be a variant of uncertain significance.

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