ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3308G>A (p.Arg1103Lys)

gnomAD frequency: 0.00001  dbSNP: rs200371555
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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 RCV004564308 SCV000819797 uncertain significance Familial adenomatous polyposis 1 2024-12-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1103 of the APC protein (p.Arg1103Lys). This variant is present in population databases (rs200371555, 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: 570983). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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 RCV001019844 SCV001181252 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-06 criteria provided, single submitter clinical testing The p.R1103K variant (also known as c.3308G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 3308. The arginine at codon 1103 is replaced by lysine, an amino acid with highly similar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV003999572 SCV004843113 uncertain significance Classic or attenuated familial adenomatous polyposis 2024-03-05 criteria provided, single submitter clinical testing

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