ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1333C>G (p.Gln445Glu)

dbSNP: rs876658802
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217057 SCV000274512 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-31 criteria provided, single submitter clinical testing The p.Q445E variant (also known as c.1333C>G), located in coding exon 10 of the APC gene, results from a C to G substitution at nucleotide position 1333. The glutamine at codon 445 is replaced by glutamic acid, 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.
CeGaT Center for Human Genetics Tuebingen RCV000585258 SCV000693182 uncertain significance not provided 2017-10-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000585258 SCV000693993 uncertain significance not provided 2017-06-05 criteria provided, single submitter clinical testing Variant summary: The APC c.1333C>G (p.Gln445Glu) variant causes a missense change involving the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). The variant of interest is absent in a large, broad control population, ExAC in 120462 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS).
Color Diagnostics, LLC DBA Color Health RCV000217057 SCV000904772 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003475011 SCV001374523 uncertain significance Familial adenomatous polyposis 1 2024-09-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 445 of the APC protein (p.Gln445Glu). 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: 230838). 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.
Fulgent Genetics, Fulgent Genetics RCV002494587 SCV002802058 uncertain significance Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach 2022-05-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV003475011 SCV004202659 uncertain significance Familial adenomatous polyposis 1 2023-08-09 criteria provided, single submitter clinical testing
GeneDx RCV000585258 SCV005080899 uncertain significance not provided 2023-10-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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