ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2413C>T (p.Arg805Ter) (rs587779783)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168336 SCV000219025 pathogenic Familial adenomatous polyposis 1 2020-04-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Arg805*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2039 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with familial adenomatous polyposis (PMID: 20649969, 8730280, 19531215, 20924072, 20223039, 30897307). ClinVar contains an entry for this variant (Variation ID: 127281). This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). 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.
Ambry Genetics RCV000115073 SCV000273569 pathogenic Hereditary cancer-predisposing syndrome 2019-02-25 criteria provided, single submitter clinical testing The p.R805* pathogenic mutation (also known as c.2413C>T) located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 2413. This changes the amino acid from an arginine to a stop codon within coding exon 15. This variant was previously described in an individual with severe polyposis and a family history of colorectal cancer (<span style="font-size:12.8000001907349px">Dobbie Z et al. J. Med. Genet. 1996 Apr; 33(4):274-80). It was also seen in two juvenile FAP patients (Gutierrez Sanchez LH et al. Gastrointest. Endosc. 2018 Mar;87(3):648-656.e3). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501097 SCV000591111 pathogenic Familial multiple polyposis syndrome 2015-09-01 criteria provided, single submitter clinical testing
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV001270020 SCV001450443 pathogenic not provided 2019-10-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV001292808 SCV001481466 pathogenic Desmoid disease, hereditary 2020-10-15 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 8730280, 30897307; ClinVar 127281]
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001270020 SCV001742857 pathogenic not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV001270020 SCV001953278 pathogenic not provided no assertion criteria provided clinical testing

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