Submissions for variant NM_000642.3(AGL):c.854G>A (p.Arg285Gln)

gnomAD frequency: 0.00026  dbSNP: rs144817648

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000434478	SCV000527439	uncertain significance	not provided	2018-02-14	criteria provided, single submitter	clinical testing	The R285Q variant in the AGL gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R285Q variant was not observed at any significant frequency in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R285Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R285Q as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000548159	SCV000626770	uncertain significance	Glycogen storage disease type III	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 285 of the AGL protein (p.Arg285Gln). This variant is present in population databases (rs144817648, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with AGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 385974). 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 AGL protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Genome-Nilou Lab	RCV000548159	SCV002055089	uncertain significance	Glycogen storage disease type III	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004022401	SCV004872487	uncertain significance	Inborn genetic diseases	2021-06-11	criteria provided, single submitter	clinical testing	The c.854G>A (p.R285Q) alteration is located in exon 7 (coding exon 6) of the AGL gene. This alteration results from a G to A substitution at nucleotide position 854, causing the arginine (R) at amino acid position 285 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000548159	SCV001457969	uncertain significance	Glycogen storage disease type III	2019-12-16	no assertion criteria provided	clinical testing
Center for Computational Biology & Bioinformatics, University of California, San Diego	RCV004567914	SCV005050101	uncertain significance	Meniere disease	2024-06-03	no assertion criteria provided	research