ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5392A>G (p.Asn1798Asp) (rs200794097)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035077 SCV000058717 uncertain significance not specified 2010-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000034417 SCV000209532 uncertain significance not provided 2018-06-25 criteria provided, single submitter clinical testing This variant is denoted APC c.5392A>G at the cDNA level, p.Asn1798Asp (N1798D) at the protein level, and results in the change of an Asparagine to an Aspartic Acid (AAT>GAT). This variant was observed in 1/430 individuals with atherosclerosis, with no specific information about cancer history (Johnston 2012). APC Asn1798Asp was not observed at a significant allele frequency in large population cohorts (Lek 2016). APC Asn1798Asp is located in the beta-catenin binding domain and the SAMP repeats/axin binding domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether APC Asn1798Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000167996 SCV000218647 uncertain significance Familial adenomatous polyposis 1 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 1798 of the APC protein (p.Asn1798Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs200794097, ExAC 0.06%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 41532). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000167996 SCV000488327 uncertain significance Familial adenomatous polyposis 1 2016-03-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491791 SCV000579863 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000035077 SCV000600115 uncertain significance not specified 2017-04-19 criteria provided, single submitter clinical testing
Color RCV000491791 SCV000681736 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-04 criteria provided, single submitter clinical testing
Mendelics RCV000167996 SCV000838133 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034417 SCV000043132 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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