ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3173A>G (p.Asp1058Gly) (rs148725540)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120013 SCV000148988 likely benign not specified 2017-12-19 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.
Ambry Genetics RCV000115079 SCV000172904 benign Hereditary cancer-predisposing syndrome 2014-07-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Co-occurence with mutation in same gene (phase unknown)
Invitae RCV000034408 SCV000219052 benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000350760 SCV000452001 likely benign APC-Associated Polyposis Disorders 2016-06-14 criteria provided, single submitter clinical testing
Counsyl RCV000168362 SCV000487857 uncertain significance Familial adenomatous polyposis 1 2015-11-24 criteria provided, single submitter clinical testing
Color RCV000115079 SCV000681584 likely benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000034408 SCV000805389 likely benign not provided 2017-08-28 criteria provided, single submitter clinical testing
Mendelics RCV000168362 SCV000838099 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034408 SCV000887516 benign not provided 2017-08-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000120013 SCV000916492 likely benign not specified 2018-07-02 criteria provided, single submitter clinical testing Variant summary: APC c.3173A>G (p.Asp1058Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0006 in 276366 control chromosomes. The observed variant frequency is greater than 8-fold above 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 benign. c.3173A>G has been reported in the literature in individuals affected with Familial Adenomatous Polyposis without evidence for pathogenicity. Co-occurrence with other pathogenic variants have been reported (UMD - APC c.2016_2017delTA, p.His672GlnfsX7; Kerr_2013 - unspecified), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 with conflicting interpretations, including VUS (1x), likely benign (3x), and benign (1x). Based on the evidence outlined above, the variant was classified as likely benign.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034408 SCV000043118 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ITMI RCV000120013 SCV000084143 not provided not specified 2013-09-19 no assertion provided reference population
True Health Diagnostics RCV000115079 SCV000805207 likely benign Hereditary cancer-predisposing syndrome 2018-05-09 no assertion criteria provided clinical testing

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