ClinVar Miner

Submissions for variant NM_000038.6(APC):c.417_418AG[2] (p.Arg141fs) (rs1554069850)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534073 SCV000647502 pathogenic Familial adenomatous polyposis 1 2017-05-09 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 4 of the APC mRNA (c.421_422delAG), causing a frameshift at codon 141. This creates a premature translational stop signal (p.Arg141Valfs*6) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in APC are known to be pathogenic (PMID: 20685668, 17963004). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000657261 SCV000778991 pathogenic not provided 2016-09-20 criteria provided, single submitter clinical testing This deletion of two nucleotides in APC is denoted c.421_422delAG at the cDNA level and p.Arg141ValfsX6 (R141VfsX6) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AGAG[delAG]GTAA. The deletion causes a frameshift which changes an Arginine to a Valine at codon 141, and creates a premature stop codon at position 6 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. Although this variant has not, to our knowledge, been published in the literature as a germline variant, it has been reported as a confirmed somatic variant in colorectal cancer (Liu 2007). Based on the currently available evidence, we consider this deletion to be a likely pathogenic variant.

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