ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5772del (p.Lys1924fs)

dbSNP: rs1554086974
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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 RCV004563403 SCV000768131 pathogenic Familial adenomatous polyposis 1 2018-11-08 criteria provided, single submitter clinical testing 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 (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 sequence change results in a premature translational stop signal in the APC gene (p.Lys1924Asnfs*46). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 920 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals from a family affected with desmoid tumors and gastrointestinal polyps, as well as in individuals affected with familial adenomatous polyposis (FAP) (PMID: 17426470, 20685668). In addition, this variant has been reported in individuals in the Universal Mutation Database (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 537473). For these reasons, this variant has been classified as Pathogenic.

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