ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1239dup (p.Arg414fs) (rs879254088)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235625 SCV000293416 pathogenic not provided 2016-03-14 criteria provided, single submitter clinical testing This duplication of one nucleotide in APC is denoted c.1239dupA at the cDNA level and p.Arg414ThrfsX5 (R414TfsX5) at the protein level. The normal sequence, with the base that is duplicated in braces, is AGAT[A]CGCG. The duplication causes a frameshift which changes an Arginine to a Threonine at codon 414, and creates a premature stop codon at position 5 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC c.1239dupA has been identified in multiple individuals with colonic polyps, as well as duodenal cancer, pancreatic cancer, and hepatoblastoma (Andresen 2009, Kerr 2013). We consider this variant to be pathogenic.
Invitae RCV000465130 SCV000552616 pathogenic Familial adenomatous polyposis 1 2018-01-23 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 10 of the APC mRNA (c.1239dupA), causing a frameshift at codon 414. This creates a premature translational stop signal (p.Arg414Thrfs*5) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic. This particular variant has been reported in the literature in families affected with familial adenomatous polyposis (PMID: 19444466, 23159591). For these reasons, this variant has been classified as Pathogenic.

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