ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3577_3578del (p.Gln1193fs) (rs1060503326)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462186 SCV000552650 pathogenic Familial adenomatous polyposis 1 2018-08-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Gln1193Valfs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1651 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals and families affected with familial adenomatous polyposis (FAP) (PMID: 7746201, 8730280, 20685668, 20223039, 9067764, 1843350). ClinVar contains an entry for this variant (Variation ID: 411475). This variant is expected to delete a large portion of the C-terminal region of the APC protein, including the basic domain, the EB1 binding site, and the HDLG binding site, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). Although functional studies have not been performed for this variant, different truncating variants (p.Ser1276* and p.Glu1309Aspfs*4) that lie downstream of this variant have been determined to be pathogenic (PMID: 18433509, 9452101, 20223039, 1316610, 23159591, 24664542). 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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