ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6977G>A (p.Arg2326Gln) (rs531178000)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129062 SCV000183763 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000480098 SCV000567817 uncertain significance not provided 2016-06-13 criteria provided, single submitter clinical testing This variant is denoted APC c.6977G>A at the cDNA level, p.Arg2326Gln (R2326Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Arg2326Gln was not observed at a significant allele frequency in 1000 Genomes. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. APC Arg2326Gln occurs at a position where amino acids with properties similar to Arginine are tolerated across species and is located in the located in the basic domain and a Ser-rich region (Azzopardi 2008, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether APC Arg2326Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000530076 SCV000647682 uncertain significance Familial adenomatous polyposis 1 2018-11-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2326 of the APC protein (p.Arg2326Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs531178000, ExAC 0.01%). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 140854). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on APC function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000129062 SCV000905995 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-15 criteria provided, single submitter clinical testing

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