ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3847G>C (p.Ala1283Pro)

dbSNP: rs1428789824
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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 RCV000584035 SCV000686954 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000584035 SCV002623603 uncertain significance Hereditary cancer-predisposing syndrome 2025-02-06 criteria provided, single submitter clinical testing The p.A1283P variant (also known as c.3847G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 3847. The alanine at codon 1283 is replaced by proline, an amino acid with highly 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. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV005091481 SCV005787386 uncertain significance Familial adenomatous polyposis 1 2024-05-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1283 of the APC protein (p.Ala1283Pro). 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: 490270). 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.

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