Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV005638532 | SCV006324411 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2025-08-12 | criteria provided, single submitter | curation | This classification follows the ClinGen ACMG TP53 v1.4.0 classification scheme; We chose these criteria: PS3 (medium pathogenic): Funk et al. PMID: 39774325 deleterious, PS4 (supporting pathogenic): This variant has been reported in an individual meeting Chompret criteria for Li Fraumeni syndrome (Saucier E et al. Pediatr Blood Cancer, 2024 Dec;71:e31362) -> PS4: we recommend that probands with TP53 germline variants meeting Revised Chompret should be given 0.5 point (…) -> PS4_sup, PM2 (supporting pathogenic): absent from gnomAD v4/3/2, PP3 (supporting pathogenic): BayesDel = 0.6431 (thus > 0.16), PP4 (supporting pathogenic): This variant was detected in at least one individual at an allele fraction that is suggestive of clonal hematopoiesis, a predictor of TP53 pathogenicity (Ambry internal data; Fortuno C et al. Genet Med. 2022 03;24:673-680) |
| Ambry Genetics | RCV005286207 | SCV005951600 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2025-02-21 | criteria provided, single submitter | clinical testing | The c.652_654delGTG variant (also known as p.V218del) is located in coding exon 5 of the TP53 gene. This variant results from an in-frame GTG deletion at nucleotide positions 652 to 654. This results in the in-frame deletion of a valine at codon 218. This variant has been reported in an individual meeting Chompret criteria for Li Fraumeni syndrome (Saucier E et al. Pediatr Blood Cancer, 2024 Dec;71:e31362). This variant was detected in at least one individual at an allele fraction that is suggestive of clonal hematopoiesis, a predictor of TP53 pathogenicity (Ambry internal data; Fortuno C et al. Genet Med. 2022 03;24:673-680). In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV005092343 | SCV005776339 | pathogenic | Li-Fraumeni syndrome | 2024-10-31 | criteria provided, single submitter | clinical testing | This variant, c.652_654del, results in the deletion of 1 amino acid(s) of the TP53 protein (p.Val218del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 634761). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the DNA binding domain which is critical for DNA binding activity (PMID: 26205489). While functional studies have not been performed to directly test the effect of this variant on TP53 protein function, this suggests that disruption of this region of the protein is causative of disease. This variant disrupts a region of the TP53 protein in which other variant(s) (p.Val218Met) have been determined to be pathogenic (internal data). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV004027348 | SCV004933536 | 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]. |
| German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000785492 | SCV000924064 | pathogenic | Ovarian neoplasm | 2018-12-01 | no assertion criteria provided | research |