ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.740A>G (p.Asn247Ser) (rs786201762)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000457243 SCV000545342 uncertain significance Li-Fraumeni syndrome 2016-08-07 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 247 of the TP53 protein (p.Asn247Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. 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. This missense change is located in a region of the TP53 protein where a significant number of previously reported TP53 missense mutations are found (PMID: 9926936) and is located within the DNA binding domain, which is important for proper TP53 protein function (PMID: 26205489) . These observations suggest that this previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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