ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.353C>T (p.Thr118Ile) (rs1064794141)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484765 SCV000567956 uncertain significance not provided 2016-06-23 criteria provided, single submitter clinical testing This variant is denoted TP53 c.353C>T at the cDNA level, p.Thr118Ile (T118I) at the protein level, and results in the change of a Threonine to an Isoleucine (ACA>ATA). TP53 Thr118Ile has been reported as a somatic variant in breast cancer (Holstege 2009, Lo Nigro 2012). TP53 Thr118Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Threonine and Isoleucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. TP53 Thr118Ile occurs at a position that is conserved across species and is located in the DNA binding domain (Bode 2004). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether TP53 Thr118Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000526166 SCV000629806 uncertain significance Li-Fraumeni syndrome 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 118 of the TP53 protein (p.Thr118Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID:  (Variation ID: 419837). An experimental study in yeast has shown that this missense change does not affect TP53 transactivation activity (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.
Ambry Genetics RCV000569220 SCV000664386 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence

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