Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001066845 | SCV001231866 | uncertain significance | Li-Fraumeni syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TP53-related conditions. 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. This variant has been reported to have conflicting or insufficient data to determine the effect on TP53 protein function (PMID: 12826609). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with threonine at codon 382 of the TP53 protein (p.Lys382Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. |
| Ambry Genetics | RCV003160552 | SCV003856779 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-07 | criteria provided, single submitter | clinical testing | The p.K382T variant (also known as c.1145A>C), located in coding exon 10 of the TP53 gene, results from an A to C substitution at nucleotide position 1145. The lysine at codon 382 is replaced by threonine, an amino acid with similar properties. Studies conducted in human cell lines indicate this alteration is proficient at growth suppression and has no dominant negative effect (Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This variant is reported to have partially functional transactivation in yeast based assays (Kato S et al. Proc Natl Acad Sci U S A, 2003 Jul;100:8424-9). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003467836 | SCV004206235 | uncertain significance | Adrenocortical carcinoma, hereditary | 2023-09-06 | criteria provided, single submitter | clinical testing |