ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5145del (p.Asp1715fs) (rs863225363)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204668 SCV000259326 pathogenic Familial adenomatous polyposis 1 2017-11-15 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide in exon 16 of the APC mRNA (c.5145delC), causing a frameshift at codon 1715. This creates a premature translational stop signal (p.Asp1715Glufs*29) 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 individuals affected with familial adenomatous polyposis (PMID: 23159591). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000491031 SCV000579781 pathogenic Hereditary cancer-predisposing syndrome 2018-03-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000202072 SCV000778919 pathogenic not provided 2017-07-05 criteria provided, single submitter clinical testing This deletion of one nucleotide in APC is denoted c.5145delC at the cDNA level and p.Asp1715GlufsX29 (D1715EfsX29) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATGA[delC]AATA. The deletion causes a frameshift which changes an Aspartic Acid to a Glutamic Acid at codon 1715, and creates a premature stop codon at position 29 of the new reading frame. This variant is predicted to cause loss of normal protein function through protein truncation. The disrupted region at the end of the gene includes the 20-aa repeat beta-catenin down-regulating domain, the SAMP repeats/axin binding domain, the basic domain, the EB1 binding domain, and the hDLG binding domain (Azzopardi 2008). APC Asp1715GlufsX29 has been reported in at least two individuals undergoing APC genetic testing in a clinical laboratory (Kerr 2013). We consider this variant to be pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202072 SCV000257010 likely pathogenic not provided no assertion criteria provided clinical testing

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