Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492658 | SCV000581133 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-11-01 | criteria provided, single submitter | clinical testing | The c.1179dupC variant, located in coding exon 10 of the TP53 gene, results from a duplication of C at nucleotide position 1179, causing a translational frameshift with a predicted alternate stop codon. Per ACMG guidelines this variant could be interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med 2008;10:294); however this duplication and subsequent frameshift occur near the 3' terminus of TP53 and result in the elongation of the protein by 76 amino acids (p.*394Lext*76). The exact functional impact of these inserted amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002523988 | SCV003327690 | likely pathogenic | Li-Fraumeni syndrome | 2022-09-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 428888). This protein extension has been observed in individual(s) with breast cancer (Invitae). In at least one individual the variant was observed to be de novo. This sequence change disrupts the translational stop signal of the TP53 mRNA. It is expected to extend the length of the TP53 protein by 76 additional amino acid residues. |