Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002524697 | SCV003255718 | pathogenic | Li-Fraumeni syndrome | 2023-05-24 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 376636). This missense change has been observed in individual(s) with TP53-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). 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). For these reasons, this variant has been classified as Pathogenic. 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; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 22109999, 29979965, 30224644). |
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]. |
Cancer Genetics Lab, |
RCV002509381 | SCV002819262 | pathogenic | Acute myeloid leukemia | no assertion criteria provided | clinical testing |