ClinVar Miner

Submissions for variant NM_000038.6(APC):c.607C>G (p.Gln203Glu) (rs141576417)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115109 SCV000186254 benign Hereditary cancer-predisposing syndrome 2015-08-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with mutation in same gene (phase unknown),Other data supporting benign classification,Other strong data supporting benign classification,General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034394 SCV000043106 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Color RCV000115109 SCV000681776 likely benign Hereditary cancer-predisposing syndrome 2016-09-19 criteria provided, single submitter clinical testing
GeneDx RCV000120051 SCV000149018 benign not specified 2018-01-31 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.
GenomeConnect, ClinGen RCV000709878 SCV000840215 not provided Desmoid disease, hereditary; Familial adenomatous polyposis 1 no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
ITMI RCV000120051 SCV000084187 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000034394 SCV000694089 likely benign not provided 2017-01-03 criteria provided, single submitter clinical testing Variant summary: APC c.607C>G variant affects a conserved nucleotide, resulting in amino acid change from a neutral Gln residue to a negatively charged Glu residue. 4/5 in-silico tools predict this variant to be damaging, however these in silico predictions have not been verified with functional studies. This variant has not been cited in patients from the literature, but is found in 63/114606 control chromosomes at a frequency of 0.0005497, which is about 9 times of maximal expected frequency of a pathogenic allele (0.0000602), suggesting this variant is benign. In addition, multiple diagnostic clinical laboratories classified this variant as likely benign. An internal specimen has a co-occurrence with a deleterious BRCA1 variant, further support for a the benign nature of the variant. Taken together, this was classified as likely benign until additional information is available.
Invitae RCV000122789 SCV000166046 benign Familial adenomatous polyposis 1 2018-01-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000120051 SCV000538294 likely benign not specified 2016-12-14 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: This variant is present in 1.2% of Ashkenazi Jewish alleles in gnomAD (121/10150). Frequency too high for disease. It is classified in ClinVar with 1 star as Likely benign/benign by Invitae and Ambry and as VUS by GeneDx and Biesecker lab.
PreventionGenetics RCV000034394 SCV000805445 likely benign not provided 2017-09-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034394 SCV000888754 benign not provided 2018-05-08 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000115109 SCV000693485 likely benign Hereditary cancer-predisposing syndrome 2017-09-28 no assertion criteria provided clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000757929 SCV000886450 likely benign Familial multiple polyposis syndrome 2018-05-29 criteria provided, single submitter research The APC variant designated as NM_000038.5:c.607C>G (p.Gln203Glu) is classified as likely benign. This variant is found in approximately 1 out of 500 individuals of European ancestry (exac.broadinstitute.org), which is a higher frequency than expected of a pathogenic APC variant (Kobayashi et al, 2017, PMID:28166811). It is listed in the ClinVar database (Variation ID: 41509) and has been classified as benign or likely benign by 7 clinical laboratories. In one obseved family, this variant was identified in two members who have been documented to have fewer than 5 colon polyps on colonoscopy. Bayesian analysis integrating all of this data (Tavtigian et al, 2018, PMID: 29300386) gives about 1% probability of pathogenicity, which is consistent with a classification of likely benign. This variant is not predicted to alter APC function or modify cancer risk. A modest (less than 2-fold) increase in risk of cancer or colon polyps due to this variant cannot be excluded. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study.

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