Submissions for variant NM_000152.5(GAA):c.1555A>G (p.Met519Val)

dbSNP: rs1598581919

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001379276	SCV001577047	pathogenic	Glycogen storage disease, type II	2021-03-05	criteria provided, single submitter	clinical testing	This variant disrupts the p.Met519 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14695532, 31193175, 31342611). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects GAA protein function (PMID: 7866409, 19862843). 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. This variant has been observed in individual(s) with Pompe disease (PMID: 7866409). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 519 of the GAA protein (p.Met519Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine.
AiLife Diagnostics, AiLife Diagnostics	RCV002223308	SCV002501132	uncertain significance	not provided	2021-05-26	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV002223308	SCV003828440	uncertain significance	not provided	2020-05-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001379276	SCV004197856	likely pathogenic	Glycogen storage disease, type II	2023-03-11	criteria provided, single submitter	clinical testing