ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4612_4613del (p.Glu1538fs) (rs387906236)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000646319 SCV000768087 pathogenic Familial adenomatous polyposis 1 2018-10-05 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Glu1538Ilefs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1,306 amino acids (46%) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with familial adenomatous polyposis (PMID: 8162051, 20223039, 20513532, 20685668, 21643010, 21779980, 22987206). This variant has been reported in individuals in the Universal Mutation Database (PMID: 8594558). This variant results in the removal of functional domains 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). Different truncations downstream of this variant, p.Tyr2645Lysfs*14 and p.Asp1942Glufs*27, have been determined to be pathogenic (PMID: 1316610, 8381579, 9824584, 22135120, 15108286, 11001924). 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. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000866 SCV000021016 pathogenic Gardner syndrome 1997-01-01 no assertion criteria provided literature only

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