ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.672G>A (p.Glu224=) (rs267605076)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567974 SCV000665290 likely pathogenic Hereditary cancer-predisposing syndrome 2017-01-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,Last nucleotide of exon,Functionally-validated splicing mutation,Other data supporting pathogenic classification
Invitae RCV000800846 SCV000940585 pathogenic Li-Fraumeni syndrome 2018-09-06 criteria provided, single submitter clinical testing This sequence change affects codon 224 of the TP53 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TP53 protein. This variant also falls at the last nucleotide of exon 6 of the TP53 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed as de novo in an individual affected with Li-Fraumeni syndrome associated tumors (PMID: 28475293). ClinVar contains an entry for this variant (Variation ID: 80709). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this silent change promotes aberrant splicing, resulting in a 5 nucelotides insertion and a frameshift in the TP53 gene (PMID: 24630730). For these reasons, this variant has been classified as Pathogenic.
MutSpliceDB: a database of splice sites variants effects on splicing,NIH RCV000786830 SCV000925724 not provided not provided no assertion provided in vitro

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