Submissions for variant NM_000038.6(APC):c.4987G>A (p.Glu1663Lys)

dbSNP: rs758987855

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003765280	SCV000254019	uncertain significance	Familial adenomatous polyposis 1	2024-11-04	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1663 of the APC protein (p.Glu1663Lys). 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: 216168). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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	RCV000568323	SCV000667460	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-18	criteria provided, single submitter	clinical testing	The p.E1663K variant (also known as c.4987G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 4987. The glutamic acid at codon 1663 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mendelics	RCV002247624	SCV002516886	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002478702	SCV002777960	uncertain significance	Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach	2021-11-10	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000568323	SCV004361475	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-07	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with lysine at codon 1663 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.
Baylor Genetics	RCV003765280	SCV005052573	uncertain significance	Familial adenomatous polyposis 1	2023-11-26	criteria provided, single submitter	clinical testing