Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001042929 | SCV001206638 | pathogenic | Li-Fraumeni syndrome | 2023-10-25 | criteria provided, single submitter | clinical testing | This variant, c.529_546del, results in the deletion of 6 amino acid(s) of the TP53 protein (p.Pro177_Cys182del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of TP53-related conditions (PMID: 29489754, 33138793, 33245408). ClinVar contains an entry for this variant (Variation ID: 840834). This variant disrupts a region of the TP53 protein in which other variant(s) (p.Pro177Arg) have been determined to be pathogenic (PMID: 12826609, 20421238, 26787237, 27501770, 27873457, 30224644; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV003160297 | SCV003856778 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | The c.529_546del18 variant (also known as p.P177_C182del) is located in coding exon 4 of the TP53 gene. This variant results from an in-frame deletion of 18 nucleotides (CCCCACCATGAGCGCTGC) at nucleotide positions 529 to 546. This results in the in-frame deletion of 6 amino acids (PHHERC) at codons 177 to 182. This alteration was detected in a cohort of 2538 Chinese breast cancer patients who tested negative for BRCA1/2 mutations (Kwong A et al. BMC Cancer, 2020 Nov;20:1053), as well as in a cohort of 1876 well-defined familial HBOC index patients from Germany who were tested negative for a germline BRCA1/2 mutations (Grill S et al. Arch Gynecol Obstet, 2021 Jun;303:1557-1567). These amino acid positions are generally well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |