Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000792342 | SCV000931631 | pathogenic | Li-Fraumeni syndrome | 2022-03-06 | criteria provided, single submitter | clinical testing | Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt TP53 protein function. This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 281 of the TP53 protein (p.Asp281Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with osteosarcoma (PMID: 25293557). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 376585). Experimental studies have shown that this missense change affects TP53 function (PMID: 7651740, 12826609). This variant disrupts the p.Asp281 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10864200, 15925506, 17572079, 23894400). 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. |
| Myriad Genetics, |
RCV004022209 | SCV004932240 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-20 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 7651740]. This variant is expected to disrupt protein structure [Myriad internal data]. |