ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.146A>G (p.Asp49Gly) (rs759728549)

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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 RCV000219898 SCV000274888 uncertain significance Hereditary cancer-predisposing syndrome 2015-03-30 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000702036 SCV000830864 uncertain significance Li-Fraumeni syndrome 2018-04-08 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 49 of the TP53 protein (p.Asp49Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs759728549, ExAC 0.002%). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 231133). An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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