Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001037944 | SCV001201382 | uncertain significance | Li-Fraumeni syndrome | 2019-02-15 | criteria provided, single submitter | clinical testing | 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. An experimental study in yeast has shown that this variant partially impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). This variant has not been reported in the literature in individuals with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with methionine at codon 111 of the TP53 protein (p.Leu111Met). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and methionine. |
| Ambry Genetics | RCV003307811 | SCV003998797 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-26 | criteria provided, single submitter | clinical testing | The p.L111M variant (also known as c.331C>A), located in coding exon 3 of the TP53 gene, results from a C to A substitution at nucleotide position 331. The leucine at codon 111 is replaced by methionine, an amino acid with highly similar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have partially functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is proficient at growth suppression and has no dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). 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. |