Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004564384 | SCV000828450 | uncertain significance | Familial adenomatous polyposis 1 | 2018-02-07 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with APC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.His2770Glnfs*4). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 74 amino acids of the APC protein. |
| Ambry Genetics | RCV002424684 | SCV002679328 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-12 | criteria provided, single submitter | clinical testing | The c.8310_8311delCA variant, located in coding exon 15 of the APC gene, results from a deletion of two nucleotides at nucleotide positions 8310 to 8311, causing a translational frameshift with a predicted alternate stop codon (p.H2770Qfs*4). This alteration occurs at the 3' terminus of theAPC gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 74 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. However, this alteration has not been seen in individuals with classic FAP (Ambry internal data). Clinical correlation is advised. |