Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026814 | SCV001189270 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-05-27 | criteria provided, single submitter | clinical testing | The c.7798_7801delCAAA pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of 4 nucleotides at nucleotide positions 7798 to 7801, causing a translational frameshift with a predicted alternate stop codon (p.Q2600Vfs*15). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV002552418 | SCV001591769 | pathogenic | Familial adenomatous polyposis 1 | 2024-07-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln2600Valfs*15) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 244 amino acid(s) of the APC protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 827255). This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001776090 | SCV002013899 | pathogenic | not provided | 2021-01-21 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Myriad Genetics, |
RCV002552418 | SCV004043647 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-16 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV002552418 | SCV004207995 | likely pathogenic | Familial adenomatous polyposis 1 | 2022-02-02 | criteria provided, single submitter | clinical testing |