ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6247_6250delinsTGT (p.Ile2083fs) (rs1064792978)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476655 SCV000552649 pathogenic Familial adenomatous polyposis 1 2018-06-24 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotide and inserts 3 nucleotides in exon 16 of the APC mRNA (c.6247_6250delinsTGT), causing a frameshift at codon 2083. This creates a premature translational stop signal (p.Ile2083Tyrfs*29) and is expected to result in an absent or disrupted protein product. 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, c.7932_7935del (p.Tyr2645Lysfs*14), that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). For these reasons, this variant has been classified as Pathogenic.

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