Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV005870816 | SCV006582695 | likely pathogenic | TP53-related disorder | 2025-02-28 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v4.1.0 dataset. Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.87 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 1.00 (> 0.75, sensitivity 0.96 and precision 0.92)]. The same nucleotide change resulting in the same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000584921 /PMID: 27501770). Different missense changes at the same codon (p.Ser240Arg, p.Ser240Asn) have been reported to be associated with TP53-related disorder (ClinVar ID: VCV000826894, VCV002502882). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Molecular Pathology, |
RCV000709404 | SCV006277709 | likely pathogenic | Li-Fraumeni syndrome | 2024-07-26 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002289987 | SCV002668525 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-06-24 | criteria provided, single submitter | clinical testing | The p.S240G variant (also known as c.718A>G), located in coding exon 6 of the TP53 gene, results from an A to G substitution at nucleotide position 718. The serine at codon 240 is replaced by glycine, an amino acid with 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 mutation has also been reported in a proband with Li-Fraumeni syndrome diagnosed with adrenocortical carcinoma at 1 year of age (Villani A et al. Lancet Oncol 2016 Sep;17(9):1295-305). This amino acid position is highly 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. |
| Genome- |
RCV002289986 | SCV002583026 | likely pathogenic | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV002289987 | SCV002582365 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000709404 | SCV001228935 | pathogenic | Li-Fraumeni syndrome | 2025-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 240 of the TP53 protein (p.Ser240Gly). 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: 27391063, 27501770, 34240179, 35264596, 36963804). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 584921). 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: 12826609, 29979965, 30224644). For these reasons, this variant has been classified as Pathogenic. |
| Mendelics | RCV000989712 | SCV001140254 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2019-05-28 | criteria provided, single submitter | clinical testing |