Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166212 | SCV000216991 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-01-12 | criteria provided, single submitter | clinical testing | The p.Q144P pathogenic mutation (also known as c.431A>C), located in coding exon 4 of theTP53 gene, results from an A to C substitution at nucleotide position 431. The glutamine at codon 144 is replaced by proline, an amino acid with similar properties. This variant is located in the DNA binding domain of the TP53 protein, is reported to have loss of transactivation capacity in yeast based assays (IARC TP53 database; Kato S et al.Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a 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, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Labcorp Genetics |
RCV001850338 | SCV002112810 | uncertain significance | Li-Fraumeni syndrome | 2020-11-25 | 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. Experimental studies have shown that this variant affects TP53 protein function (PMID: 12826609, 30224644, 29979965). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 186594). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with proline at codon 144 of the TP53 protein (p.Gln144Pro). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and proline. |
Genome- |
RCV000166212 | SCV002582084 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002288758 | SCV002582647 | uncertain significance | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000785331 | SCV000923899 | likely pathogenic | Ovarian neoplasm | 2018-12-01 | no assertion criteria provided | research |