Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Diagnostics Laboratory, |
RCV002348427 | SCV006324633 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-04-23 | criteria provided, single submitter | clinical testing | PVS1 (RNA), PS2, PS4_Supporting, PM2_Supporting TP53 c.560-19_560-9del is an intronic variant located close to a canonical splice site. It is not present in the population database gnomAD v2.1.1, non cancer dataset (PM2_supporting). The SpliceAI algorithm predicts that the variant impairs the splicing acceptor site of intron 5 (deltascore=0.79) and the skipping of exon 6. RNA studies have shown that this variant disrupts mRNA splicing (internal data from Myriad, Ambry, Invitae, PMID 8479743) (PVS1 (RNA)). This variant has been reported in 2 Chompret individuals affected with a TP53-related phenotype, which awards 1 point to this variant as per ClinGen SVI Recommendation for LFS/Chompret Criterion (internal data, external data) (PS4_supporting). It has been identified as de novo in a children affected with rhabdomyosarcoma (paternity was confirmed) (external data) (PS2). It has been reported in ClinVar (2x P, 1x LP), but it has not been reported in LOVD, TP53 database. Based on the currently available information, c.560-19_560-9del is classified as a pathogenic variant according to ClinGen-TP53Guidelines version 2.2. |
| Myriad Genetics, |
RCV004031834 | SCV004932530 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-15 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [Myriad internal data]. |
| Ambry Genetics | RCV002348427 | SCV002649188 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-07-29 | criteria provided, single submitter | clinical testing | The c.560-19_560-9del11 intronic pathogenic mutation begins 9 nucleotides before coding exon 5 in the TP53 gene. This variant results from a deletion of 11 nucleotides at positions c.560-9 to c.560-19. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with TP53-related disease (Ambry internal data, personal communication, Felix CA et al. Oncogene, 1993 May;8:1203-10). This variant has been determined to be the result of a de novo mutation or germline mosaicism in at least one individual exhibiting features of a Li-Fraumeni phenotype (personal communication). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV001058103 | SCV001222647 | pathogenic | Li-Fraumeni syndrome | 2020-08-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 8479743). This variant has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (PMID: 8479743, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 853317). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 5 of the TP53 gene. It does not directly change the encoded amino acid sequence of the TP53 protein. |
| Dr. |
RCV005866776 | SCV006562886 | not provided | Gastric cancer | no classification provided | in vitro |