ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8497C>T (p.Arg2833Cys)

dbSNP: rs201459013
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000775359 SCV000909643 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-08 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 2833 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with colon cancer (PMID: 30279230), and melanoma (PMID: 29684080). This variant has been identified in 2/248236 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV003653307 SCV001396256 uncertain significance Familial adenomatous polyposis 1 2023-07-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2833 of the APC protein (p.Arg2833Cys). This variant is present in population databases (rs201459013, gnomAD 0.0009%). 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: 630205). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. 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 RCV000775359 SCV004059046 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-19 criteria provided, single submitter clinical testing The p.R2833C variant (also known as c.8497C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 8497. The arginine at codon 2833 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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