Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004562630 | SCV001199847 | pathogenic | Familial adenomatous polyposis 1 | 2019-09-14 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the APC gene (p.Ser2424Valfs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 420 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 492671). 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. |
| Ambry Genetics | RCV002384280 | SCV002672523 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | The c.7270_7273delTCAA pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of 4 nucleotides at nucleotide positions 7270 to 7273, causing a translational frameshift with a predicted alternate stop codon (p.S2424Vfs*13). This alteration occurs at the 3' terminus of theAPC gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts 14.8% of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation |
| Myriad Genetics, |
RCV004562630 | SCV004043524 | 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. |
| All of Us Research Program, |
RCV004002383 | SCV004840128 | likely pathogenic | Classic or attenuated familial adenomatous polyposis | 2023-12-12 | criteria provided, single submitter | clinical testing | The c.7270_7273del (p.Ser2424Valfs*13) variant in the APC gene is located on the exon 16 and is predicted to shift the reading frame that introduces a premature translation termination codon (p.Ser2424Valfs*13), resulting in an absent or disrupted protein product. Loss-of-function variants of APC are known to be pathogenic (PMID: 26446593, 23159591, 31591141, 33769591). The variant is reported in ClinVar (ID: 492671). The variant is absent in the general population database (gnomAD). Therefore, the c.7270_7273del (p.Ser2424Valfs*13) variant of APC gene has been classified as likely pathogenic. |
| Mayo Clinic Laboratories, |
RCV000584000 | SCV000691765 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |