Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Genomic Medicine, |
RCV005229909 | SCV005871951 | oncogenic | Neoplasm | 2025-03-04 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV002288598 | SCV004933219 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-15 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. |
| Ambry Genetics | RCV002288599 | SCV002648064 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-08-21 | criteria provided, single submitter | clinical testing | The p.L194F pathogenic mutation (also known as c.580C>T), located in coding exon 5 of the TP53 gene, results from a C to T substitution at nucleotide position 580. The leucine at codon 194 is replaced by phenylalanine, an amino acid with highly similar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have non-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 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 alteration has been observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Genome- |
RCV002288598 | SCV002583035 | likely pathogenic | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV002288599 | SCV002582374 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001377420 | SCV001574751 | likely pathogenic | Li-Fraumeni syndrome | 2025-04-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 194 of the TP53 protein (p.Leu194Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Li-Fraumeni syndrome (PMID: 21761402, 27501770, 32817165; internal data). ClinVar contains an entry for this variant (Variation ID: 127817). Invitae Evidence Modeling incorporating data from in vitro experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 9572492, 12826609, 18818522, 29979965, 30224644). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV000115728 | SCV000149637 | likely pathogenic | not provided | 2019-06-21 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect with respect to transcriptional activation, apoptosis, and growth suppression activities (Epstein 1998, Kato 2003, Marzec 2015, Kotler 2018); Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with bilateral breast or lung cancer (Melhem-Bertrandt 2012, Villani 2016); This variant is associated with the following publications: (PMID: 26181206, 18223694, 17070499, 26942128, 25733866, 26378048, 27381050, 26425688, 28580174, 27956623, 26009011, 16443602, 19429664, 12667443, 17344317, 12779080, 7935394, 10884390, 9572492, 28397142, 12826609, 29979965, 21761402, 27501770, 30720243, 30840781) |
| Key Laboratory of Carcinogenesis and Cancer Invasion, |
RCV003997297 | SCV004046824 | likely pathogenic | Adrenal cortex carcinoma | no assertion criteria provided | clinical testing |