Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001058103 | SCV001222647 | pathogenic | Li-Fraumeni syndrome | 2020-08-25 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 8479743). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002348427 | SCV002649188 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-31 | criteria provided, single submitter | clinical testing | The c.560-19_560-9del11 intronic pathogenic mutation, located in intron 4 of the TP53 gene, results from a deletion of 11 nucleotides within intron 4 of the TP53 gene. 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). RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |