Submissions for variant NM_000152.5(GAA):c.1004G>A (p.Gly335Glu)

dbSNP: rs730880022

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000156939	SCV003443317	pathogenic	Glycogen storage disease, type II	2023-07-11	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with Pompe disease (PMID: 32711049). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly335 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22644586, 31510962). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects GAA function (PMID: 22644586). 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 GAA protein function. ClinVar contains an entry for this variant (Variation ID: 180142). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 335 of the GAA protein (p.Gly335Glu).
Medical Genetic Department, Shiraz University Of Medical Science	RCV000156939	SCV000206660	pathogenic	Glycogen storage disease, type II		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579766	SCV001808447	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001579766	SCV001964592	pathogenic	not provided		no assertion criteria provided	clinical testing