Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000458661 | SCV000545279 | likely pathogenic | Li-Fraumeni syndrome | 2017-08-27 | criteria provided, single submitter | clinical testing | This sequence change is a 114 nucleotide deletion of the genomic region encompassing a portion of exon 4 and intron 4 of the TP53 gene. This deletion removes the last 93 nucleotides of exon 4 and the first 21 nucleotides of intron 4, including the splice donor site. This deletion is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with a TP53-related disease. In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. |