ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5025dup (p.Arg1676Ter) (rs878853454)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232552 SCV000282771 pathogenic Familial adenomatous polyposis 1 2016-03-28 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 16 of the APC mRNA (c.5025dupT), causing a frameshift at codon 1676. This creates a premature translational stop signal in the last exon of the APC mRNA (p.Arg1676*). While this is not anticipated to result in nonsense mediated decay, it is expected to remove the final ~1150 amino acid residues of APC, which is equivalent to ~40% of the total protein. While this particular variant has not been reported in the literature, numerous pathogenic truncating variants have been reported downstream of this c.5025dupT variant in individuals affected with classical familial adenomatous polyposis (FAP), attenuated FAP, or desmoid tumor, suggesting that the C-terminal portion of the protein is clinically important (PMID: 23159591, 8940264, 9824584, 8968744). For these reasons, this variant has been classified as Pathogenic.

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