ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5758C>G (p.Arg1920Gly) (rs587779800)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115106 SCV000149015 uncertain significance not provided 2017-05-22 criteria provided, single submitter clinical testing This variant is denoted APC c.5758C>G at the cDNA level, p.Arg1920Gly (R1920G) at the protein level, and results in the change of an Arginine to a Glycine (CGA>GGA). This variant has not, to our knowledge, been published in the literature as a germline pathogenic or benign variant. APC Arg1920Gly was observed at an allele frequency of 0.015% (1/6612) in individuals of Finnish ancestry in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Arg1920Gly occurs at a position that is conserved across species and is located in the SAMP repeats/Axin binding domain and a Beta-catenin down-regulating domain (Azzopardi 2008). In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on the currently available information, we consider APC Arg1920Gly to be a variant of uncertain significance.
Invitae RCV000549510 SCV000647606 uncertain significance Familial adenomatous polyposis 1 2017-12-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 1920 of the APC protein (p.Arg1920Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs587779800, ExAC 0.02%) but has not been reported in the literature in individuals with a APC-related disease. ClinVar contains an entry for this variant (Variation ID: 127308). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000562980 SCV000667256 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence
Color RCV000562980 SCV000681760 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-18 criteria provided, single submitter clinical testing

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