ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1240C>T (p.Arg414Cys) (rs137854567)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120052 SCV000148976 likely benign not specified 2018-01-10 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000034380 SCV000166014 benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115067 SCV000172854 benign Hereditary cancer-predisposing syndrome 2015-11-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Subpopulation frequency in support of benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,No disease association in appropriately sized case-control study(ies)
Illumina Clinical Services Laboratory,Illumina RCV000315386 SCV000451986 likely benign APC-Associated Polyposis Disorders 2016-06-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000120052 SCV000538298 uncertain significance not specified 2017-01-25 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency too high for disease. Max MAF in ExAC: 0.19% (13 Finnish alleles and 90 European alleles) and gnomAD: 0.18% (47 Finnish alleles and 129 European alleles). Penetrance of APC is close to 100%. It has been reported in affected and unaffected individuals. It is classified in ClinVar as Benign by Invitae and Ambry, and as VUS by Biesecker, CSER, Pathway genomics, GeneDx.
Color RCV000115067 SCV000681448 likely benign Hereditary cancer-predisposing syndrome 2016-10-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000034380 SCV000693992 benign not provided 2017-06-05 criteria provided, single submitter clinical testing Variant summary: The APC c.1240C>T (p.Arg414Cys) variant causes a missense change involving the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. However, a functional study found that this variant maintained inhibitory activity on the transcription mediated by the beta-catenin/TCF4 complex, as did wild-type APC. The variant of interest has been found in a large, broad control population, ExAC in 105/120892 control chromosomes at a frequency of 0.0008685, which is approximately 12 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this variant is likely a benign polymorphism. This variant was found in multiple studies in FAP patients (van der Klift_PMS2_Hum Mutat_2016, Azzopardi_CancerRsrch_2008) but one functional study and the high frequency in population suggests a benign effect. In addition, multiple clinical diagnostic laboratories/reputable databases recently classified this variant as likely benign/benign. Taken together, this variant is classified as benign.
Counsyl RCV000122757 SCV000786455 likely benign Familial adenomatous polyposis 1 2018-05-15 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000034380 SCV000805365 likely benign not provided 2017-09-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034380 SCV000887503 likely benign not provided 2019-02-12 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034380 SCV000892420 likely benign not provided 2018-04-01 criteria provided, single submitter clinical testing
OMIM RCV000000833 SCV000020983 pathogenic Gardner syndrome 1991-08-09 no assertion criteria provided literature only
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034380 SCV000043109 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ITMI RCV000120052 SCV000084188 not provided not specified 2013-09-19 no assertion provided reference population
Pathway Genomics RCV000122757 SCV000189870 uncertain significance Familial adenomatous polyposis 1 2014-07-24 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000122757 SCV000190063 uncertain significance Familial adenomatous polyposis 1 2014-06-01 no assertion criteria provided research
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000120052 SCV000691712 likely benign not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000115067 SCV000886658 likely benign Hereditary cancer-predisposing syndrome 2018-10-04 no assertion criteria provided clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761025 SCV000890940 uncertain significance Pilocytic astrocytoma 2016-08-05 no assertion criteria provided clinical testing

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