Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001068346 | SCV001233453 | pathogenic | Li-Fraumeni syndrome | 2019-04-01 | criteria provided, single submitter | clinical testing | This missense change (p.Gly245Asp) has been reported to segregate with Li Fraumeni syndrome-associated cancers in a single family (PMID: 2259385) and also has been reported in individuals affected with chronic lymphocytic leukemia and chronic-phase primary myelofibrosis (PMID: 21232794, 22052707). This variant disrupts the p.Gly245 amino acid residue in TP53. Other variant(s) that disrupt this residue (p.Gly245Ser) have been determined to be pathogenic (PMID: 12826609, 20522432, 11370630, 1565143, 24122735, 17311302). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 245 of the TP53 protein (p.Gly245Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |