ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1409-1G>C

dbSNP: rs863225313
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003771229 SCV001577447 pathogenic Familial adenomatous polyposis 1 2023-12-05 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 11 of the APC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with familial adenomatous polyposis (PMID: 9950360, 10612827, 15459959, 19036155; Invitae). ClinVar contains an entry for this variant (Variation ID: 1068153). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003771229 SCV004045219 likely pathogenic Familial adenomatous polyposis 1 2023-05-01 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
All of Us Research Program, National Institutes of Health RCV004803677 SCV005424291 likely pathogenic Classic or attenuated familial adenomatous polyposis 2024-03-24 criteria provided, single submitter clinical testing This variant causes a G to C nucleotide substitution at the -1 position in intron 11 of the APC gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with APC-related disorders in the literature. Different variants impacting the same canonical acceptor site, c.1409-1G>T, c.1409-1G>A, c.1409-2A>G, and c.1409-2A>T, are known to be disease-causing (ClinVar variation ID: 217927, 433621, 517442, 490202). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

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