ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5425A>G (p.Lys1809Glu)

dbSNP: rs1580660009
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001024084 SCV001186042 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-15 criteria provided, single submitter clinical testing The p.K1809E variant (also known as c.5425A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 5425. The lysine at codon 1809 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002552380 SCV001404118 uncertain significance Familial adenomatous polyposis 1 2024-09-23 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1809 of the APC protein (p.Lys1809Glu). 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: 825724). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV002552380 SCV004015258 uncertain significance Familial adenomatous polyposis 1 2023-07-07 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 1809 of the APC protein (p.Lys1809Glu). 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 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Therefore, it has been classified as a Variant of Uncertain Significance.

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