ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4984A>G (p.Ile1662Val)

gnomAD frequency: 0.00001  dbSNP: rs1434584091
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002234570 SCV000768108 uncertain significance Familial adenomatous polyposis 1 2023-10-05 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1662 of the APC protein (p.Ile1662Val). 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: 537460). 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. 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 RCV000771691 SCV000904322 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-03 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1662 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 RCV000771691 SCV004059031 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-29 criteria provided, single submitter clinical testing The p.I1662V variant (also known as c.4984A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 4984. The isoleucine at codon 1662 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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