Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Genomic Medicine, |
RCV005230307 | SCV005871942 | likely oncogenic | Neoplasm | 2025-03-04 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV004022231 | SCV004930571 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-16 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 20505364, 29979965]. This variant is expected to disrupt protein structure [Myriad internal data]. |
| Labcorp Genetics |
RCV002524697 | SCV003255718 | pathogenic | Li-Fraumeni syndrome | 2025-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 237 of the TP53 protein (p.Met237Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with TP53-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 376636). Invitae Evidence Modeling incorporating data from in vitro 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 affects TP53 function (PMID: 12826609, 22109999, 29979965, 30224644). This variant disrupts the p.Met237 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11370630, 12826609, 17606709, 21343334, 29979965, 30224644; internal data). 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. |
| Cancer Genetics Lab, |
RCV002509381 | SCV002819262 | pathogenic | Acute myeloid leukemia | no assertion criteria provided | clinical testing |