ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1786T>C (p.Ser596Pro)

dbSNP: rs1561568258
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002533443 SCV000824924 uncertain significance Familial adenomatous polyposis 1 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 596 of the APC protein (p.Ser596Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
GeneDx RCV001756210 SCV002007456 uncertain significance not provided 2019-09-25 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002397424 SCV002714402 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-16 criteria provided, single submitter clinical testing The p.S596P variant (also known as c.1786T>C), located in coding exon 14 of the APC gene, results from a T to C substitution at nucleotide position 1786. The serine at codon 596 is replaced by proline, an amino acid with similar properties. This variant has been detected in patients with a personal history of polyposis (Ambry internal data). 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.

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