Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271881 | SCV002556051 | likely pathogenic | Li-Fraumeni syndrome | 2022-06-21 | criteria provided, single submitter | clinical testing | Variant summary: TP53 c.1028delA (p.Glu343GlyfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251040 control chromosomes. c.1028delA has been reported in the literature in individuals affected with breast cancer (Bortolini Silveira_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Ambry Genetics | RCV002382492 | SCV002692296 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-02-09 | criteria provided, single submitter | clinical testing | The c.1028delA pathogenic mutation, located in coding exon 9 of the TP53 gene, results from a deletion of one nucleotide at nucleotide position 1028, causing a translational frameshift with a predicted alternate stop codon (p.E343Gfs*2). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Color Diagnostics, |
RCV002382492 | SCV004359973 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-29 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 10 of the TP53 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |