Submissions for variant NM_000038.6(APC):c.2978A>T (p.Lys993Met)

dbSNP: rs1554084627

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003634199	SCV004559527	uncertain significance	Familial adenomatous polyposis 1	2023-08-11	criteria provided, single submitter	clinical testing	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 lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 993 of the APC protein (p.Lys993Met). 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. 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV004596607	SCV005090691	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing