Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001226488 | SCV001398803 | uncertain significance | Li-Fraumeni syndrome | 2019-07-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with glutamine at codon 285 of the TP53 protein (p.Glu285Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Li-Fraumeni syndrome (PMID: 10697617). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Glu285 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11051239, 22507745, 23894400, 18762572, 25584008). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been reported to have conflicting or insufficient data to determine the effect on TP53 protein function (PMID: 21343334, 12826609). |