Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000541004 | SCV001142558 | pathogenic | Li-Fraumeni syndrome | 2024-08-05 | reviewed by expert panel | curation | The NM_000546.6 c.372C>A (p.Cys124Ter) is a TP53 nonsense variant upstream of p.Lys351. The variant is predicted to undergo nonsense-mediated decay (PVS1; PMID: 22233476). This variant has been identified as a de novo occurrence with unconfirmed parental relationships in 2 individuals with LFS-associated cancers totaling 4 phenotype points (PS2; PMID: 22233476, 32658383). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for Li Fraumeni Syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: PVS1, PS2, PM2_Supporting. (Bayesian Points: 13; VCEP specifications version 2.0; 7/24/2024). |
Labcorp Genetics |
RCV000541004 | SCV000629807 | pathogenic | Li-Fraumeni syndrome | 2023-09-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys124*) in the TP53 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with childhood adrenocortical carcinoma (PMID: 22233476). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 458537). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV004023787 | SCV004933347 | pathogenic | Li-Fraumeni syndrome 1 | 2024-02-13 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |