Description
Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 16508005, 17401428, 27533082). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Thr125 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12826609, 25503501, 26014290, 26845104). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 376667). This missense change has been observed in individuals with Li-Fraumeni syndrome (PMID: 18511570, 20127978, 20522432, 29753700; Invitae; externalcommunication). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 125 of the TP53 protein (p.Thr125Arg).
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
