ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2674G>T (p.Glu892Ter)

dbSNP: rs1561578889
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004564389 SCV000829238 pathogenic Familial adenomatous polyposis 1 2018-02-24 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Glu892*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1952 amino acids of the APC protein. This variant has been reported in a family affected with familial adenomatous polyposis (PMID: 12010888). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (ExAC no frequency). This variant removes the basic domain, the EB1 binding site, and the HDLG binding site, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). Other truncations downstream of this variant,  p.Tyr932*, p.Tyr935*, and p.Gln1062*, have been reported in individuals affected with familial adenomatous polypsis (PMID: 1338764, 20685668, 10090483, 1316610, 8162022). While functional studies have not been performed to directly test the effect of this variant on APC protein function, these observations suggest that deletion of the C-terminal portion of the APC protein is causative of disease.
GeneDx RCV004702345 SCV005201643 pathogenic not provided 2023-10-19 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 37795928, 8381579, 9824584, 1316610, 15311282, 22135120, 17293347, 27081525, 12010888)

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