ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.440T>A (p.Val147Asp)

dbSNP: rs1453167097
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002051460 SCV002114385 uncertain significance Li-Fraumeni syndrome 2021-07-03 criteria provided, single submitter clinical testing 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 variant affects TP53 protein function (PMID: 12826609, 29979965, 30224644). 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. This variant has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 147 of the TP53 protein (p.Val147Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid.
Baylor Genetics RCV003464164 SCV004206278 uncertain significance Adrenocortical carcinoma, hereditary 2023-05-23 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004038887 SCV004932680 likely pathogenic Li-Fraumeni syndrome 1 2024-02-14 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].

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