ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4360A>G (p.Lys1454Glu) (rs111866410)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000200964 SCV000149001 benign not specified 2016-05-27 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 RCV000987572 SCV000153821 benign Familial adenomatous polyposis 1 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115092 SCV000186657 benign Hereditary cancer-predisposing syndrome 2015-01-20 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238996 SCV000297022 uncertain significance Familial multiple polyposis syndrome 2015-10-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000264340 SCV000452011 likely benign APC-Associated Polyposis Disorders 2016-06-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000200964 SCV000538293 likely benign not specified 2016-08-12 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 high for disorder; multiple papers question pathogenicity
Integrated Genetics/Laboratory Corporation of America RCV000586737 SCV000694052 likely benign not provided 2016-09-16 criteria provided, single submitter clinical testing Variant summary: The APC c.4360A>G (p.Lys1454Glu) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant. This variant is not located in any known domain/repeat (InterPro). This variant was found in 68/123380 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0053867 (56/10396). This frequency is about 75 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In literature, the variant has also been reported in patients of various cancer phenotypes (such as FAP, prostate cancer, hepatic cancer, CRC, bladder cancer and B-cell lymphoma) including somatic occurrences, however, without strong evidence for causality. One functional study showed that this variant has a normal effect in an in vitro beta-cateninregulated transcription (CRT) assay (Azzopardi_2008). Multiple clinical labs have classified this variant as benign/likely benign (3 labs) to uncertain significance (1 lab and 1 database). Taken together, this variant has currently been classified as a Likely Benign.
PreventionGenetics,PreventionGenetics RCV000200964 SCV000805408 benign not specified 2017-06-09 criteria provided, single submitter clinical testing
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV000200964 SCV000864337 likely benign not specified 2017-09-05 criteria provided, single submitter clinical testing BS1, BP6; This alteration has an allele frequency that is greater than expected for the associated disease, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Color RCV000115092 SCV000902616 benign Hereditary cancer-predisposing syndrome 2016-03-22 criteria provided, single submitter clinical testing
Mendelics RCV000987572 SCV001136911 benign Familial adenomatous polyposis 1 2019-05-28 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148365 SCV000190057 uncertain significance Colorectal adenoma 2014-06-01 no assertion criteria provided research

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