ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6257C>G (p.Pro2086Arg)

dbSNP: rs786202975
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166066 SCV000216828 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-10 criteria provided, single submitter clinical testing The p.P2086R variant (also known as c.6257C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 6257. The proline at codon 2086 is replaced by arginine, an amino acid with dissimilar 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. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000515279 SCV000611339 uncertain significance Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma 2017-05-23 criteria provided, single submitter clinical testing
Counsyl RCV000205730 SCV000785536 uncertain significance Familial adenomatous polyposis 1 2017-09-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000205730 SCV002257567 uncertain significance Familial adenomatous polyposis 1 2024-07-25 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2086 of the APC protein (p.Pro2086Arg). 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: 186466). 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 with a negative predictive value of 95%. 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.
Myriad Genetics, Inc. RCV000205730 SCV004017814 uncertain significance Familial adenomatous polyposis 1 2023-02-16 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
GeneDx RCV005230013 SCV005874884 uncertain significance not provided 2024-08-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 36243179)

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