ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5245C>G (p.Gln1749Glu)

dbSNP: rs1765893831
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002562623 SCV001399798 uncertain significance Familial adenomatous polyposis 1 2019-10-15 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 1749 of the APC protein (p.Gln1749Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV001751441 SCV002005420 uncertain significance not provided 2019-05-13 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 that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV002562623 SCV004205338 uncertain significance Familial adenomatous polyposis 1 2023-06-15 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003584863 SCV004363126 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-16 criteria provided, single submitter clinical testing This missense variant replaces glutamine with glutamic acid at codon 1749 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV003584863 SCV005033091 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-09 criteria provided, single submitter clinical testing The p.Q1749E variant (also known as c.5245C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 5245. The glutamine at codon 1749 is replaced by glutamic acid, 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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