Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001220864 | SCV001392876 | likely pathogenic | Li-Fraumeni syndrome | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 119 of the TP53 protein (p.Ala119Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features consistent with Li-Fraumeni Syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 949408). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 29979965, 30224644). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |