ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4385_4386AG[3] (p.Glu1464fs) (rs387906234)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474620 SCV000552497 pathogenic Familial adenomatous polyposis 1 2018-08-16 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides from exon 16 of the APC mRNA (c.4391_4394delAGAG), causing a frameshift at codon 1464. This creates a premature translational stop signal in the last exon of the APC mRNA (p.Glu1464Valfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated APC protein. 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 (FAP) (PMID: 20685668, 15108286, 16088911, 21643010, 20223039, 23159591). In one individual, this variant was reported to arise as a de novo sequence change (PMID: 15108286). In addition, multiple pathogenic loss-of-function variants have been identified downstream of this sequence change in exon 16 of the APC gene.  ClinVar contains an entry for this variant (Variation ID: 812). For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500484 SCV000591171 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing
Ambry Genetics RCV000565829 SCV000676354 pathogenic Hereditary cancer-predisposing syndrome 2016-12-12 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)
GeneKor MSA RCV000565829 SCV000821695 pathogenic Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
OMIM RCV000000851 SCV000021001 pathogenic Periampullary adenoma 1993-11-01 no assertion criteria provided literature only

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