ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1743+1G>A (rs761458613)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226069 SCV000282703 likely pathogenic Familial adenomatous polyposis 1 2019-07-19 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 14. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (ExAC <0.01%). This variant has been observed in several individuals affected with familial adenomatous polyposis (PMID: 19029688, Invitae). This variant is also known as IVS13+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 236563). Donor and acceptor splice site variants 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV000484492 SCV000568271 likely pathogenic not provided 2017-02-13 criteria provided, single submitter clinical testing This variant is denoted APC c.1743+1G>A or IVS14+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 14 of the APC gene. Using alternate nomenclature, this variant would be defined as APC IVS13+1G>A. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in at least one individual reported to have Familial Adenomatous Polyposis, although specific clinical phenotype information was not provided (Plawski 2008). Based on the currently available information, we consider APC c.1743+1G>A to be a likely pathogenic variant.

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