ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4463T>G (p.Leu1488Ter)

dbSNP: rs786202324
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002553451 SCV002150937 pathogenic Familial adenomatous polyposis 1 2020-12-22 criteria provided, single submitter clinical testing 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 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. This sequence change creates a premature translational stop signal (p.Leu1488*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1356 amino acid(s) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of familial adenomatosis polyposis (PMID: 19444466, 20685668).
Myriad Genetics, Inc. RCV002553451 SCV004045403 pathogenic Familial adenomatous polyposis 1 2023-05-11 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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