ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.392A>T (p.Asn131Ile) (rs1131691037)

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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 RCV000492742 SCV000581162 likely pathogenic Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes),Other data supporting pathogenic classification
Invitae RCV000821569 SCV000962331 uncertain significance Li-Fraumeni syndrome 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces asparagine with isoleucine at codon 131 of the TP53 protein (p.Asn131Ile). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Li-Fraumeni syndrome (PMID: 19556618, 19127094). This variant has also been reported as 13071A>T in the literature. ClinVar contains an entry for this variant (Variation ID: 428902). An experimental study in yeast has shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). 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.

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