ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2365C>T (p.Gln789Ter) (rs398123117)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000490954 SCV000579835 pathogenic Hereditary cancer-predisposing syndrome 2016-04-29 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)
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000657603 SCV000226391 pathogenic not provided 2013-01-07 criteria provided, single submitter clinical testing
GeneDx RCV000657603 SCV000779344 pathogenic not provided 2018-03-14 criteria provided, single submitter clinical testing This variant is denoted APC c.2365C>T at the cDNA level and p.Gln789Ter (Q789X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through protein truncation. This variant has been reported in individuals with familial adenomatous polyposis (Lagarde 2010) and is considered pathogenic.
Invitae RCV000174978 SCV000552546 pathogenic Familial adenomatous polyposis 1 2018-06-22 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Gln789*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2055 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with familial adenomatous polyposis (PMID: 20685668) and in an individual affected with colorectal cancer (PMID: 28975465). This variant is also known as c.2311C>T (p.Gln771*) in the literature. ClinVar contains an entry for this variant (Variation ID: 92341). Different truncations (p.Arg876* and p.Gln879*) that lie downstream of this variant have been determined to be pathogenic (PMID: 10094547, 8187091, 12581900, 20223039, 19029688). 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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