Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003534487 | SCV000825275 | pathogenic | Familial adenomatous polyposis 1 | 2023-07-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp2504*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 340 amino acid(s) of the APC protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of APC-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 218007). 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. |
Myriad Genetics, |
RCV002517338 | SCV004043980 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-16 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Baylor Genetics | RCV002517338 | SCV004207928 | pathogenic | Familial adenomatous polyposis 1 | 2022-06-09 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000201984 | SCV000257032 | likely pathogenic | not provided | no assertion criteria provided | research | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000201984 | SCV002035658 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000201984 | SCV002037576 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
de |
RCV002517338 | SCV004022257 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-07-21 | no assertion criteria provided | research | The variant NM_000038.6:c.7511G>A (chr5:112843105) in APC was detected in 1 heterozygote out of 58K WGS Icelanders (MAF= 0,001%). This variant has been reported in ClinVar previously as pathogenic. Based on ACMG criteria (PVS1, PM2) this variant classifies as likely pathogenic. |