ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4240del (p.Met1413_Val1414insTer)

dbSNP: rs1580645606
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003337339 SCV000939307 pathogenic Familial adenomatous polyposis 1 2018-09-10 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. For these reasons, this variant has been classified as Pathogenic. Other variant(s) that disrupt this region (p.Tyr2645Lysfs*14) have been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with APC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Val1414*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1430 amino acids of the APC protein.
Ambry Genetics RCV002332620 SCV002630539 pathogenic Hereditary cancer-predisposing syndrome 2017-10-17 criteria provided, single submitter clinical testing The c.4240delG pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of one nucleotide at nucleotide position 4240, causing a translational frameshift with a predicted alternate stop codon (p.V1414*). 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. RCV003337339 SCV004043110 pathogenic Familial adenomatous polyposis 1 2023-05-10 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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