ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4440G>C (p.Gln1480His)

dbSNP: rs876659881
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564996 SCV000667597 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-09 criteria provided, single submitter clinical testing The p.Q1480H variant (also known as c.4440G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 4440. The glutamine at codon 1480 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003537142 SCV000830710 uncertain significance Familial adenomatous polyposis 1 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1480 of the APC protein (p.Gln1480His). 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: 482375). 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.
Color Diagnostics, LLC DBA Color Health RCV000564996 SCV001342183 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-17 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 1480 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268184 SCV002550624 uncertain significance not specified 2024-02-06 criteria provided, single submitter clinical testing
GeneDx RCV003222044 SCV003918386 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528, 27533247)
Baylor Genetics RCV002528059 SCV004206638 uncertain significance Familial adenomatous polyposis 1 2023-05-02 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677759 SCV000803915 uncertain significance Intrahepatic cholangiocarcinoma 2017-08-16 no assertion criteria provided clinical testing

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