ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5827_5828insAA (p.Arg1943fs) (rs1554087023)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538571 SCV000647611 pathogenic Familial adenomatous polyposis 1 2017-04-28 criteria provided, single submitter clinical testing This sequence change inserts 2 nucleotides in exon 16 of the APC mRNA (c.5827_5828insAA), causing a frameshift at codon 1943. This creates a premature translational stop signal in the last exon of the APC mRNA (p.Arg1943Lysfs*28). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 873 amino acids of the APC protein, which accounts for 31% of the full length protein. Loss-of-function variants in APC are known to be pathogenic (PMID: 20685668, 17963004). This particular variant has been reported in the literature in an individual affected with familial adenomatous polyposis (PMID: 21779980). A different truncation downstream of this variant (p.Asn1979Thrfs*64) has been determined to be pathogenic (PMID: 20434453, 9824584, 26681312). 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.

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