Submissions for variant NM_000038.6(APC):c.6853G>A (p.Val2285Ile)

dbSNP: rs1554087794

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000584052	SCV000687097	uncertain significance	Hereditary cancer-predisposing syndrome	2019-02-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000779721	SCV000916482	uncertain significance	not specified	2018-02-16	criteria provided, single submitter	clinical testing	Variant summary: APC c.6853G>A (p.Val2285Ile) results in a conservative amino acid change located in the Adenomatous polyposis coli protein basic domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 121016 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.6853G>A in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV000584052	SCV001187977	uncertain significance	Hereditary cancer-predisposing syndrome	2019-08-14	criteria provided, single submitter	clinical testing	The p.V2285I variant (also known as c.6853G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 6853. The valine at codon 2285 is replaced by isoleucine, 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.
Invitae	RCV002530773	SCV001216948	uncertain significance	Familial adenomatous polyposis 1	2023-08-17	criteria provided, single submitter	clinical testing	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. 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. ClinVar contains an entry for this variant (Variation ID: 490345). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2285 of the APC protein (p.Val2285Ile).