ClinVar Miner

Submissions for variant NM_000038.6(APC):c.147_150del (p.Lys49fs) (rs587781694)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129859 SCV000184676 pathogenic Hereditary cancer-predisposing syndrome 2017-12-07 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 RCV000497263 SCV000209574 pathogenic not provided 2014-09-12 criteria provided, single submitter clinical testing This deletion of 4 nucleotides in APC is denoted c.147_150delACAA at the cDNA level and p.Lys49AsnfsX20 (K49NfsX20) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TTAA[ACAA]CTAC. The deletion causes a frameshift, which changes a Lysine to an Asparagine at codon 49, and creates a premature stop codon at position 20 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC c.147_150delACAA, previously reported as 145delAAAC, has been observed in association with Familial Adenomatous Polyposis (Gomez-Fernandez 2009, Rivera 2011). we consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502854 SCV000591015 pathogenic Familial adenomatous polyposis 2013-12-13 criteria provided, single submitter clinical testing
Invitae RCV000552842 SCV000647180 pathogenic Familial adenomatous polyposis 1 2018-11-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys49Asnfs*20) in the APC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with colon polyps, attenuated adenomatous polyposis (AFAP) and familial adenomatous polyposis (FAP) (PMID: 19531215, 26681312, 20924072). ClinVar contains an entry for this variant (Variation ID: 141368). Loss-of-function variants in APC are known to be pathogenic (PMID: 20685668, 17963004). For these reasons, this variant has been classified as Pathogenic.
Molecular Oncology Laboratory,Hospital Clínico San Carlos RCV000552842 SCV000844923 pathogenic Familial adenomatous polyposis 1 2018-06-01 no assertion criteria provided clinical testing

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