Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Myriad Genetics, |
RCV003141828 | SCV004933431 | pathogenic | Li-Fraumeni syndrome 1 | 2025-02-18 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 9792154, 35419288]. mRNA analysis has demonstrated abnormal mRNA splicing occurs [PMID: 9792154, 35419288]. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003141828 | SCV003806806 | likely pathogenic | Li-Fraumeni syndrome 1 | 2022-08-15 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 strong, PM2 moderated |
| Labcorp Genetics |
RCV000812930 | SCV000953260 | pathogenic | Li-Fraumeni syndrome | 2021-03-16 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 3 of the TP53 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with Li-Fraumeni syndrome (PMID: 9242456, 9792154, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 656497). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |