ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4647del (p.Glu1550fs) (rs879254283)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235328 SCV000294051 likely pathogenic not provided 2016-03-09 criteria provided, single submitter clinical testing This deletion of one nucleotide in APC is denoted c.4647delA at the cDNA level and p.Glu1550ArgfsX15 (E1550RfsX15) at the protein level. The normal sequence, with the base that is deleted in braces, is ACCA[A]GAGA. The deletion causes a frameshift which changes a Glutamic Acid to an Arginine at codon 1550, and creates a premature stop codon at position 15 of the new reading frame. Even though this frameshift occurs in the last exon of the gene, and nonsense-mediated decay is not expected to occur, it is significant since the last 1294 amino acids are replaced with 14 incorrect amino acids. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through protein truncation. We consider this variant to be likely pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV001192833 SCV001361213 likely pathogenic Familial adenomatous polyposis 2019-09-13 criteria provided, single submitter clinical testing Variant summary: APC c.4647delA (p.Glu1550ArgfsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250072 control chromosomes (gnomAD). To our knowledge, no occurrence of c.4647delA in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000235328 SCV000691752 likely pathogenic not provided no assertion criteria provided clinical testing

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