ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3469_3470GA[2] (p.Arg1158fs) (rs786203020)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467218 SCV000552748 pathogenic Familial adenomatous polyposis 1 2016-09-11 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotide from exon 16 of the APC mRNA (c.3473_3474delGA), causing a frameshift at codon 1158. This creates a premature translational stop signal in the last exon of the APC mRNA (p.Arg1158Thrfs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1,682 amino acids (~60%) of the APC protein. Loss-of-function variants in APC are known to be pathogenic. This particular variant has been reported in the literature in individuals with familial adenomatous polyposis (FAP) (PMID: 14729851, 20685668, 26446593). A different truncation downstream of this variant (p.Lys1199Glufs*8) has been determined to be pathogenic (PMID: 7951218, 8162022, 11933206, 21779980). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000574684 SCV000675921 pathogenic Hereditary cancer-predisposing syndrome 2017-01-06 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)

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