ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4473dup (p.Ala1492fs) (rs398123122)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000790817 SCV000226394 pathogenic not provided 2013-06-25 criteria provided, single submitter clinical testing Frameshift: Variant is of a type predicted to cause disease.
Invitae RCV000174979 SCV000768190 pathogenic Familial adenomatous polyposis 1 2018-01-11 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Ala1492Cysfs*22). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1352 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 92347). This variant results in the removal of functional domains of the APC protein, including the basic domain, the EB1 binding site, and the HDLG binding site, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). A different truncation (p.Glu1538Ilefs*5) that lies downstream of this variant has been determined to be pathogenic (PMID: 8162051, 20223039, 20513532, 20685668, 21643010, 21779980, 22987206). 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.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000722013 SCV000853186 pathogenic Desmoid tumor 2016-05-16 criteria provided, single submitter clinical testing This is a duplication of coding position 4473 (insertion of a T) and is predicted to change an Alanine to a Cysteine at codon 1492, shift the reading frame and result in a premature stop codon 22 amino acids downstream

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