ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.551A>G (p.Asp184Gly) (rs1060501209)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462657 SCV000545357 uncertain significance Li-Fraumeni syndrome 2016-07-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 184 of the TP53 protein (p.Asp184Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TP53-related disease. An experimental co-expression study has shown that this missense change partially restores function of TP53 proteins harboring a different loss-of-function missense change (PMID: 17417775). A separate study testing TP53 transactivation activity of 8 different promoters classifies this missense change as functional (PMID: 12826609). Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change that does not impair protein function in vitro, but is predicted by in silico methods to affect mRNA splicing. In the absence of further supportive evidence, it has been classified as a Variant of Uncertain Significance.

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