Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000633359 | SCV000754581 | pathogenic | Li-Fraumeni syndrome | 2017-10-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. Donor and acceptor splice site variants 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 sequence change removes the last 3 nucleotides of exon 8, and affects a donor splice site in intron 8 of the TP53 gene. It is expected to disrupt RNA splicing and/or create a premature translational stop signal, and likely results in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. 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. |
| Ambry Genetics | RCV002377366 | SCV002685736 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-04 | criteria provided, single submitter | clinical testing | The c.917_919+10DEL13 alteration is a deletion beginning in exon 8 of the TP53 gene and extending 10 nucleotides into intron 8. This results in the deletion of a total of 13 nucleotides, including the last 3 nucleotides of exon 8 and the first ten nucleotides of the splice donor site of intron 8. This deletion may cause a disruption of normal RNA splicing; however, direct evidence is unavailable. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |