ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6124T>C (p.Cys2042Arg) (rs730881254)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000211924 SCV000209536 uncertain significance not provided 2014-09-17 criteria provided, single submitter clinical testing This variant is denoted APC c.6124T>C at the cDNA level, p.Cys2042Arg (C2042R) at the protein level, and results in the change of a Cysteine to an Arginine (TGT>CGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Cys2042Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Cysteine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Cys2042Arg occurs at a position that is highly conserved across species and is located in SAMP repeat/axin binding domain (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether APC Cys2042Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000159564 SCV000217127 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000536382 SCV000647628 uncertain significance Familial adenomatous polyposis 1 2018-11-25 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 2042 of the APC protein (p.Cys2042Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 181812). 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.
Color RCV000159564 SCV000905992 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-14 criteria provided, single submitter clinical testing

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