Submissions for variant NM_000038.6(APC):c.5789A>C (p.Gln1930Pro)

dbSNP: rs879254254

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236296	SCV000293981	uncertain significance	not provided	2016-02-19	criteria provided, single submitter	clinical testing	This variant is denoted APC c.5789A>C at the cDNA level, p.Gln1930Pro (Q1930P) at the protein level, and results in the change of a Glutamine to a Proline (CAA>CCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Gln1930Pro was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Gln1930Pro occurs at a position that is not conserved and is located within the 20-amino acid repeat beta-catenin down regulating domain and the axin binding domain (Azzopardi 2008). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether APC Gln1930Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae	RCV003743694	SCV004382562	uncertain significance	Familial adenomatous polyposis 1	2023-11-17	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1930 of the APC protein (p.Gln1930Pro). 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: 246427). 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 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.