ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1892_1904delinsAAT (p.Ile631fs) (rs863225319)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227617 SCV000282706 pathogenic Familial adenomatous polyposis 1 2016-06-25 criteria provided, single submitter clinical testing This sequence change deletes 13 nucleotides and inserts 3 nucleotides in exon 15 of the APC mRNA (c.1892_1904delTTATTGAAAGTGGinsAAT), causing a frameshift at codon 631. This creates a premature translational stop signal (p.Ile631Lysfs*2) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in APC are known to be pathogenic (PMID: 20685668, 17963004). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192828 SCV001361207 likely pathogenic Familial multiple polyposis syndrome 2019-06-24 criteria provided, single submitter clinical testing Variant summary: APC c.1892_1904delinsAAT (p.Ile631LysfsX2) 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 (c.2547_2550delTAGA, p.Asp849fsX11; c.3183_3187delACAAA, p.Gln1062fsX1; c.3927_3931delAAAGA, p.Glu1309fsX4). The variant was absent in 251346 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1892_1904delinsAAT in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000202093 SCV000256933 likely pathogenic not provided no assertion criteria provided research

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