ClinVar Miner

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

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217961 SCV000277037 likely pathogenic Hereditary cancer-predisposing syndrome 2017-12-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Invitae RCV000540263 SCV000647196 likely pathogenic Familial adenomatous polyposis 1 2017-05-19 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 14 of the APC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been reported in the literature in an individual affected with familial adenomatous polyposis (PMID: 20685668). ClinVar contains an entry for this variant (Variation ID: 232800). A different variant affecting this nucleotide (c.1743+1G>A) has been determined to be likely pathogenic (PMID: 19029688). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function variants in APC are known to be pathogenic (PMID: 20685668, 17963004). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.

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