ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3579_3582del (p.Gln1193fs)

dbSNP: rs2149894773
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004564785 SCV002157955 pathogenic Familial adenomatous polyposis 1 2021-07-20 criteria provided, single submitter clinical testing This variant is also known as c.3578_3581del. 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. For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 14729851). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln1193Hisfs*71) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1651 amino acid(s) of the APC protein.

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