ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2804dup (p.Tyr935Ter) (rs863225332)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410020 SCV000488316 likely pathogenic Familial adenomatous polyposis 1 2016-02-25 criteria provided, single submitter clinical testing
GeneDx RCV000202260 SCV000568275 pathogenic not provided 2018-05-29 criteria provided, single submitter clinical testing This duplication of one nucleotide is denoted APC c.2804dupA at the cDNA level and p.Tyr935Ter (Y935X) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ACTT[dupA]CAAT. The duplication creates a nonsense variant, which changes a Tyrosine to a premature stop codon, and is predicted to cause loss of normal protein function through protein truncation. Even though this nonsense variant occurs in the last exon of the gene, and nonsense-mediated decay is not expected to occur, it is significant since the last 1909 amino acids are no longer translated. APC c.2804dupA, previously reported as APC 2803insA, has been shown to result in a truncated protein by a protein truncation assay (Scarano 1999) and has been reported in association with familial adenomatous polyposis (FAP) (Scarano 1999, De Rosa 2003, Lagarde 2010, Kerr 2013, Kohda 2016, Pearlman 2016). This variant is considered pathogenic.
Ambry Genetics RCV000490899 SCV000579798 pathogenic Hereditary cancer-predisposing syndrome 2017-06-08 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),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000410020 SCV000829754 pathogenic Familial adenomatous polyposis 1 2019-01-03 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Tyr935*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1909 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with familial adenomatous polyposis (PMID: 10090483, 20685668, 28533537, 23159591). This variant is also known as c.2803insA in the literature. ClinVar contains an entry for this variant (Variation ID: 217954). A different truncation (p.Gln1062*) that lies downstream of this variant has been determined to be pathogenic (PMID: 1316610, 8162022, 15771908). 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.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202260 SCV000256954 pathogenic not provided no assertion criteria provided research

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