ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1660C>T (p.Arg554Ter)

dbSNP: rs137854573
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129303 SCV000184065 pathogenic Hereditary cancer-predisposing syndrome 2022-01-13 criteria provided, single submitter clinical testing The p.R554* pathogenic mutation (also known as c.1660C>T), located in coding exon 13 of the APC gene, results from a C to T substitution at nucleotide position 1660. This changes the amino acid from an arginine to a stop codon within coding exon 13. This mutation has been reported in multiple individuals diagnosed with familial adenomatous polyposis (FAP) or attenuated FAP (AFAP) (Fodde R et al. Genomics, 1992 Aug;13:1162-8; Ripa R et al. Eur J Hum Genet, 2002 Oct;10:631-7; Friedl W et al. Hered Cancer Clin Pract, 2005 Sep;3:95-114; Truta B et al. Fam Cancer, 2005;4:127-33; Filipe B et al. Clin Genet, 2009 Sep;76:242-55; Lagarde A et al. J Med Genet, 2010 Oct;47:721-2; Rivera B et al. Ann Oncol, 2011 Apr;22:903-909; de Oliveira JC et al. Cancer Med, 2019 05;8:2114-2122; Staninova-Stojovska M et al. Balkan J Med Genet, 2019 Dec;22:5-16). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
University of Washington Department of Laboratory Medicine, University of Washington RCV000210172 SCV000266005 pathogenic Colorectal cancer, susceptibility to 2015-11-20 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000844608 SCV000271308 pathogenic Familial multiple polyposis syndrome 2021-06-28 criteria provided, single submitter clinical testing The p.Arg554X variant in APC has been previously reported in at least 15 individuals with familial adenomatous polyposis (FAP) (Fodde 1992, Ripa 2002, Friedl 2005, Rivera 2011, Bisgaard 2004, Truta 2005) and was absent from large population studies. It has also been reported in ClinVar (Variation ID#807). This nonsense variant leads to a premature termination codon at position 554, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the APC gene is an established disease mechanism in individuals with FAP. In summary, this variant meets criteria to be classified as pathogenic for familial adenomatous polyposis in an autosomal dominant manner. ACMG/AMP Criteria applied: PVS1, PS4, PM2_Supporting.
GeneDx RCV000482405 SCV000567480 pathogenic not provided 2018-04-06 criteria provided, single submitter clinical testing This variant is denoted APC c.1660C>T at the cDNA level and p.Arg554Ter (R554X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with Familial Adenomatous Polyposis (FAP) (Fodde 1992, van der Luijt 1997, Blaker 2003, Friedl and Aretz 2005, Castellsague 2010) and is considered pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000000845 SCV000647193 pathogenic Familial adenomatous polyposis 1 2024-01-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg554*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 1324223, 12357334, 15108286, 15951963, 20223039, 20685668, 20924072). ClinVar contains an entry for this variant (Variation ID: 807). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV000129303 SCV000686849 pathogenic Hereditary cancer-predisposing syndrome 2020-03-03 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 14 of the APC gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with familial adenomatous polyposis (PMID: 1324223, 7524601, 10077047, 12357334, 15951963, 16680592, 19793053, 20223039, 20685668, 20924072, 21643010, 21779980, 26622826, 26845104). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000763541 SCV000894354 pathogenic Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV000000845 SCV002761773 pathogenic Familial adenomatous polyposis 1 2022-01-11 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000000845 SCV004043967 pathogenic Familial adenomatous polyposis 1 2023-05-02 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000000845 SCV005387775 pathogenic Familial adenomatous polyposis 1 2024-11-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg554*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 1324223, 12357334, 15108286, 15951963, 20223039, 20685668, 20924072). ClinVar contains an entry for this variant (Variation ID: 807) classified as pathogenic by multiple submitters, no conflicts. For these reasons, this variant has been classified as Pathogenic
OMIM RCV000000845 SCV000020995 pathogenic Familial adenomatous polyposis 1 1992-08-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics, Yale University RCV000000845 SCV000784633 pathogenic Familial adenomatous polyposis 1 2015-11-27 no assertion criteria provided literature only
Laboratory for Genotyping Development, RIKEN RCV003162203 SCV002758123 pathogenic Gastric cancer 2021-07-01 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.