Submissions for variant NM_000038.6(APC):c.7570A>C (p.Lys2524Gln)

dbSNP: rs143060722

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000771700	SCV000904333	uncertain significance	Hereditary cancer-predisposing syndrome	2020-01-06	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with glutamine at codon 2524 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250864 chromosomes 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV004564479	SCV000934944	uncertain significance	Familial adenomatous polyposis 1	2023-09-03	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: 627838). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2524 of the APC protein (p.Lys2524Gln).
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001800868	SCV002046753	uncertain significance	not provided	2021-03-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000771700	SCV002672255	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-04	criteria provided, single submitter	clinical testing	The p.K2524Q variant (also known as c.7570A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 7570. The lysine at codon 2524 is replaced by glutamine, an amino acid with similar properties. This amino acid position is highly 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.