Submissions for variant NM_000038.6(APC):c.4879C>A (p.Gln1627Lys)

dbSNP: rs1554086263

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003538479	SCV000768187	uncertain significance	Familial adenomatous polyposis 1	2021-07-13	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine with lysine at codon 1627 of the APC protein (p.Gln1627Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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	RCV002334155	SCV002634964	uncertain significance	Hereditary cancer-predisposing syndrome	2020-03-23	criteria provided, single submitter	clinical testing	The p.Q1627K variant (also known as c.4879C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 4879. The glutamine at codon 1627 is replaced by lysine, an amino acid with similar properties. This amino acid position is 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	RCV002334155	SCV004361410	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-16	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with lysine at codon 1627 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003987643	SCV004803859	uncertain significance	not specified	2024-01-19	criteria provided, single submitter	clinical testing	Variant summary: APC c.4879C>A (p.Gln1627Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251178 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.4879C>A in individuals affected with Colorectal Cancer Risk and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 537506). Based on the evidence outlined above, the variant was classified as uncertain significance.