Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genome- |
RCV002289640 | SCV002583071 | likely pathogenic | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV002289641 | SCV002582409 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001053810 | SCV001218091 | pathogenic | Li-Fraumeni syndrome | 2019-12-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 421902). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe109Leufs*39) in the TP53 gene. It is expected to result in an absent or disrupted protein product. |
| Gene |
RCV000479264 | SCV000571235 | likely pathogenic | not provided | 2016-08-04 | criteria provided, single submitter | clinical testing | This deletion of two nucleotides in TP53 is denoted c.327_328delCC at the cDNA level and p.Phe109LeufsX39 (F109LfsX39) at the protein level. The normal sequence, with the bases that are deleted in braces, is GTTT[CC]GTCT. The deletion causes a frameshift which changes a Phenylalanine to a Leucine at codon 109, and creates a premature stop codon at position 39 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant. |