ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.516T>G (p.Val172=) (rs749309577)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000556128 SCV000629831 uncertain significance Li-Fraumeni syndrome 2018-06-08 criteria provided, single submitter clinical testing This sequence change affects codon 172 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 is present in population databases (rs749309577, ExAC 0.01%). This variant has not been reported in the literature in individuals with a TP53-related disease. 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, this variant has uncertain impact on TP53 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000578979 SCV000680591 uncertain significance not provided 2017-09-26 criteria provided, single submitter clinical testing This variant is denoted TP53 c.516T>G at the DNA level. Although this variant is silent at the codinglevel, preserving a Valine at codon 172, it is predicted to cause abnormal splicing through the creation of a new crypticsplice donor site upstream of the natural donor site. However, in the absence of RNA or functional studies, the actualeffect of this variant is unknown. While this variant has not, to our knowledge, been reported as a germline variant ithas been reported as a somatic variant in a neuroblastoma (Hosoi 1994). This variant was not observed in largepopulation cohorts (Lek 2016). The nucleotide which is altered, a thymine (T) at base 516, is not conserved. Based oncurrently available information, it is unclear whether TP53 c.516T>G is a pathogenic or benign variant. We consider itto be a variant of uncertain significance.
Ambry Genetics RCV001023655 SCV001185566 likely benign Hereditary cancer-predisposing syndrome 2018-01-25 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign

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