ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3793_3794insCTT (p.Glu1265delinsAlaTer)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000819763 SCV000960442 pathogenic Familial adenomatous polyposis 1 2018-09-11 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Val1264_Glu1265insAla*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1579 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 disease. 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.

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