ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1866C>A (p.Tyr622Ter) (rs876658355)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217597 SCV000278448 pathogenic Hereditary cancer-predisposing syndrome 2016-12-01 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)
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000504287 SCV000591093 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000584117 SCV000883405 pathogenic not provided 2018-02-15 criteria provided, single submitter clinical testing The APC c.1866C>A; p.Tyr622Ter variant (rs876658355) has been observed in individuals and families affected with familial adenomatous polyposis (FAP) ( Miyaki 1994, Miyoshi 1992, Olschwang 1993, van der Luijt 1997). This variant is reported as pathogenic in ClinVar (Variation ID: 233973) and is absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. Additionally, another variant at this codon (c.1866C>G; p.Tyr622Ter) has been reported in individuals with FAP and is considered pathogenic (Friedl 2005). This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on the above information, this variant is considered pathogenic. References: Friedl W et al. Familial Adenomatous Polyposis: Experience from a Study of 1164 Unrelated German Polyposis Patients. Hered Cancer Clin Pract. 2005; 3(3): 95–114. Miyaki M et al. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res. 1994 Jun 1;54(11):3011-20. Miyoshi Y et al. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4452-6. Olschwang S et al. Germ-line mutations in the first 14 exons of the adenomatous polyposis coli (APC) gene. Am J Hum Genet. 1993 Feb;52(2):273-9. van der Luijt R et al. Molecular analysis of the APC gene in 105 Dutch kindreds with familial adenomatous polyposis: 67 germline mutations identified by DGGE, PTT, and southern analysis. Hum Mutat. 1997;9(1):7-16.
Invitae RCV000816919 SCV000957448 pathogenic Familial adenomatous polyposis 1 2018-09-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr622*) in the APC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with familial adenomatous polyposis (PMID: 1316610, 8187091, 20685668, 8990002, 8381580). ClinVar contains an entry for this variant (Variation ID: 233973). Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000584117 SCV000691719 likely pathogenic not provided no assertion criteria provided clinical testing

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