ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3163A>G (p.Ile1055Val)

gnomAD frequency: 0.00001  dbSNP: rs1580631854
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003653390 SCV000957399 uncertain significance Familial adenomatous polyposis 1 2024-01-22 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 1055 of the APC protein (p.Ile1055Val). 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: 659813). 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.
Ambry Genetics RCV001018888 SCV001180182 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-06 criteria provided, single submitter clinical testing The p.I1055V variant (also known as c.3163A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 3163. The isoleucine at codon 1055 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well 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.
Color Diagnostics, LLC DBA Color Health RCV001018888 SCV001349721 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 1055 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 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.
Genetic Services Laboratory, University of Chicago RCV001816899 SCV002066633 uncertain significance not specified 2020-02-24 criteria provided, single submitter clinical testing DNA sequence analysis of the APC gene demonstrated a sequence change, c.3163A>G, in exon 16 that results in an amino acid change, p.Ile1055Val. This sequence change does not appear to have been previously described in patients with APC-related disorders and has also not been described in population databases (gnomAD, ExAC). The p.Ile1055Val change affects a moderately conserved amino acid residue located in a domain of the APC protein that is not known to be functional. The p.Ile1055Val substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Ile1055Val change remains unknown at this time.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.