ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2483del (p.Thr828fs) (rs886042600)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000484336 SCV000335359 pathogenic not provided 2017-09-25 criteria provided, single submitter clinical testing
GeneDx RCV000484336 SCV000564567 pathogenic not provided 2014-11-13 criteria provided, single submitter clinical testing This deletion of one nucleotide in APC is denoted c.2483delC at the cDNA level and p.Thr828IlefsX14 (T828IfsX14) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AATA[C]TACA. The deletion causes a frameshift, which changes a Threonine to an Isoleucine at codon 828, and creates a premature stop codon at position 14 of the new reading frame. This variant is predicted to cause loss of normal protein function through protein truncation. APC c.2483delC has been observed in a individual with a clinical diagnosis of familial adenomatous polyposis (Friedl 2001). we consider this variant to be pathogenic.
Ambry Genetics RCV000491139 SCV000579890 pathogenic Hereditary cancer-predisposing syndrome 2018-09-25 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000300996 SCV000768196 pathogenic Familial adenomatous polyposis 1 2017-11-10 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Thr828Ilefs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2016 amino acids (~70%) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with familial adenomatous polyposis (PMID: 11247896). ClinVar contains an entry for this variant (Variation ID: 283339). Several different truncations downstream of this variant (p.Ser932*, p.Ala1050Glufs*6, and p.Gln1062*) have been determined to be pathogenic (PMID: 20685668, 23460355, 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.

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