ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5503A>G (p.Arg1835Gly) (rs879254181)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236329 SCV000293732 uncertain significance not provided 2015-12-18 criteria provided, single submitter clinical testing This variant is denoted APC c.5503A>G at the cDNA level, p.Arg1835Gly (R1835G) at the protein level, and results in the change of an Arginine to a Glycine (AGA>GGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Arg1835Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Arg1835Gly occurs at a position where amino acids with properties similar to Arginine are tolerated across species and is located within a Beta-catenin down-regulating domain, SAMP repeats/axin binding domain, and within a Serine-rich region (Azzopardi 2008, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether APC Arg1835Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000528732 SCV000647593 uncertain significance Familial adenomatous polyposis 1 2017-06-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 1835 of the APC protein (p.Arg1835Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 246257). 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: "Benign"; 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 RCV000580701 SCV000681745 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-10 criteria provided, single submitter clinical testing

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