Submissions for variant NM_000158.4(GBE1):c.1543C>G (p.Arg515Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003787415	SCV004576426	likely pathogenic	Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic	2022-11-29	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg515 amino acid residue in GBE1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10762170, 24248152; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 GBE1 protein function. This missense change has been observed in individual(s) with GBE1-related conditions (PMID: 33517539). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 515 of the GBE1 protein (p.Arg515Gly).