Submissions for variant NM_000642.3(AGL):c.4451T>G (p.Val1484Gly)

gnomAD frequency: 0.00006  dbSNP: rs774708890

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000809505	SCV000949657	uncertain significance	Glycogen storage disease type III	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1484 of the AGL protein (p.Val1484Gly). This variant is present in population databases (rs774708890, gnomAD 0.01%). 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: 653696). 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 expected to disrupt AGL 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.
Ambry Genetics	RCV002538054	SCV003756609	uncertain significance	Inborn genetic diseases	2022-11-18	criteria provided, single submitter	clinical testing	The c.4451T>G (p.V1484G) alteration is located in exon 33 (coding exon 32) of the AGL gene. This alteration results from a T to G substitution at nucleotide position 4451, causing the valine (V) at amino acid position 1484 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV000809505	SCV004050097	uncertain significance	Glycogen storage disease type III	2023-04-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003392616	SCV004120114	uncertain significance	AGL-related condition	2023-05-25	criteria provided, single submitter	clinical testing	The AGL c.4451T>G variant is predicted to result in the amino acid substitution p.Val1484Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-100382257-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen	RCV003411789	SCV004124107	uncertain significance	not provided	2023-08-01	criteria provided, single submitter	clinical testing	AGL: PM2, BP4
Natera, Inc.	RCV000809505	SCV001459032	uncertain significance	Glycogen storage disease type III	2020-03-11	no assertion criteria provided	clinical testing