ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.747G>C (p.Arg249Ser)

dbSNP: rs28934571
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000465003 SCV000545346 uncertain significance Li-Fraumeni syndrome 2021-09-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 249 of the TP53 protein (p.Arg249Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects TP53 function (PMID: 9405613, 12826609, 15060172, 15703170, 15982667, 18477611, 20538734). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 406598). This variant has not been reported in the literature in individuals affected with TP53-related conditions.
Myriad Genetics, Inc. RCV004022606 SCV004933454 likely pathogenic Li-Fraumeni syndrome 1 2024-02-16 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 8001119, 8843196, 12509279, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].

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