ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4463dup (p.Leu1488fs)

dbSNP: rs1114167577
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003336142 SCV000822354 pathogenic Familial adenomatous polyposis 1 2022-01-17 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. ClinVar contains an entry for this variant (Variation ID: 572529). This variant is also known as 4485insT. This premature translational stop signal has been observed in individual(s) with familialadenomatous polyposis syndrome (FAP) (PMID: 10923044). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1488Phefs*26) 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.
Ambry Genetics RCV002332442 SCV002638844 pathogenic Hereditary cancer-predisposing syndrome 2020-10-23 criteria provided, single submitter clinical testing The c.4463dupT pathogenic mutation, located in coding exon 15 of the APC gene, results from a duplication of T at nucleotide position 4463, causing a translational frameshift with a predicted alternate stop codon (p.L1488Ffs*26). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003336142 SCV004044316 pathogenic Familial adenomatous polyposis 1 2023-05-11 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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