ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5912C>G (p.Ser1971Cys) (rs754691867)

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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 RCV000167000 SCV000217822 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-21 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000204602 SCV000261409 likely benign not provided 2019-03-01 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455669 SCV000538306 uncertain significance 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 has been reported in one Taiwanese individual with FAP. It is present in gnomAD with a Max MAF of 0.11% (22/18910 East Asian alleles - frequency too high for disease). This variant is classified in ClinVar with 2 stars as VUS by Ambry and Invitae.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000455669 SCV000600122 uncertain significance not specified 2017-04-28 criteria provided, single submitter clinical testing
Color RCV000167000 SCV000681769 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000455669 SCV000918490 likely benign not specified 2018-09-07 criteria provided, single submitter clinical testing Variant summary: APC c.5912C>G (p.Ser1971Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-05 in 276666 control chromosomes, predominantly at a frequency of 0.0012 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 16.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.5912C>G has been reported in the literature in East Asian individuals affected with Familial Adenomatous Polyposis and colorectal cancer (Wei_2004, Yurgelun_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, all with classifications of VUS except for one likely benign classification. Based on the evidence outlined above, the variant was classified as likely benign.
Mendelics RCV000987577 SCV001136927 uncertain significance Familial adenomatous polyposis 1 2019-05-28 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677738 SCV000803894 uncertain significance Colorectal cancer 2017-05-25 no assertion criteria provided clinical testing

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