ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4765C>G (p.Arg1589Gly) (rs72541813)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131191 SCV000186141 likely benign Hereditary cancer-predisposing syndrome 2019-03-20 criteria provided, single submitter clinical testing Internal frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Other data supporting benign classification;No disease association in small case-control study
GeneDx RCV000211915 SCV000209469 uncertain significance not provided 2017-09-13 criteria provided, single submitter clinical testing This variant is denoted APC c.4765C>G at the cDNA level, p.Arg1589Gly (R1589G) at the protein level, and results in the change of an Arginine to a Glycine (CGT>GGT). This variant has been reported in at least one individual with multiple adenomatous colon polyps (Urso 2013). However, it has also been reported in a colorectal adenoma case-control study where APC Arg1589Gly was present in 1/969 healthy control individuals, but absent in 691 polyposis cases (Azzopardi 2008). APC Arg1589Gly was observed at an allele frequency of 0.012% (8/66496) in individuals of European (Non-Finnish) ancestry in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Arg1589Gly occurs at a position that is not conserved and is located in the SAMP repeat/axin binding domain and 20-amino acid repeat beta-catenin down-regulating domain (Azzopardi 2008). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether APC Arg1589Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000232313 SCV000282762 likely benign Familial adenomatous polyposis 1 2019-12-05 criteria provided, single submitter clinical testing
Counsyl RCV000232313 SCV000489580 uncertain significance Familial adenomatous polyposis 1 2016-10-26 criteria provided, single submitter clinical testing
Color RCV000131191 SCV000681683 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-13 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000211915 SCV000805412 uncertain significance not provided 2017-03-27 criteria provided, single submitter clinical testing
Mendelics RCV000232313 SCV000838121 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001157157 SCV001318704 uncertain significance APC-Associated Polyposis Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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