ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6496C>T (p.Arg2166Ter)

dbSNP: rs764527706
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507179 SCV000600126 pathogenic not provided 2017-07-22 criteria provided, single submitter clinical testing
Invitae RCV003535802 SCV000939278 pathogenic Familial adenomatous polyposis 1 2022-03-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2166*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 678 amino acid(s) of the APC protein. 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. ClinVar contains an entry for this variant (Variation ID: 438883). This premature translational stop signal has been observed in individual(s) with colon cancer or clinical features of familial adenomatous polyposis (PMID: 14966376). This variant is not present in population databases (gnomAD no frequency).
Myriad Genetics, Inc. RCV002527337 SCV004044877 pathogenic Familial adenomatous polyposis 1 2023-05-15 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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