ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4645C>T (p.Gln1549Ter) (rs863225357)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000700753 SCV000829523 pathogenic Familial adenomatous polyposis 1 2018-06-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Gln1549*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1295 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. ClinVar contains an entry for this variant (Variation ID: 217986). This variant is expected to delete a portion of the C-terminal region of the APC protein, including the basic domain, the EB1 binding site (residues Pro2559-His2770) and the HDLG binding site (residues Ser2771-Val2843), which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). Different truncations (p.Thr1556Asnfs*3, p.Arg1943Lysfs*28 and p.Asn1979Thrfs*64) that lie downstream of this variant have been determined to be pathogenic (PMID: 9101302, 14633595, 21779980, 20434453, 9824584, 26681312). 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.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202166 SCV000257002 pathogenic not provided no assertion criteria provided research

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