ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4804C>G (p.Pro1602Ala)

dbSNP: rs1408572186
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004562029 SCV001403474 uncertain significance Familial adenomatous polyposis 1 2019-11-06 criteria provided, single submitter clinical testing 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This sequence change replaces proline with alanine at codon 1602 of the APC protein (p.Pro1602Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine.
Ambry Genetics RCV004033111 SCV005032922 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-28 criteria provided, single submitter clinical testing The p.P1602A variant (also known as c.4804C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 4804. The proline at codon 1602 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. 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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