ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6677G>A (p.Arg2226Gln)

dbSNP: rs1246580689
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004561604 SCV000647661 uncertain significance Familial adenomatous polyposis 1 2021-11-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2226 of the APC protein (p.Arg2226Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 470058). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV001025521 SCV001187723 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-16 criteria provided, single submitter clinical testing The p.R2226Q variant (also known as c.6677G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 6677. The arginine at codon 2226 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004719867 SCV005325473 uncertain significance not provided 2023-09-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528)
All of Us Research Program, National Institutes of Health RCV004806438 SCV005427835 uncertain significance Classic or attenuated familial adenomatous polyposis 2024-03-05 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003900204 SCV004712853 uncertain significance APC-related disorder 2023-11-08 no assertion criteria provided clinical testing The APC c.6677G>A variant is predicted to result in the amino acid substitution p.Arg2226Gln. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/470058/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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