Submissions for variant NM_002863.5(PYGL):c.2071G>C (p.Gly691Arg)

dbSNP: rs539898848

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000811116	SCV000951365	pathogenic	Glycogen storage disease, type VI	2021-04-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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 PYGL protein function. This variant has been observed in individual(s) with glycogen storage disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 655030). This variant is present in population databases (rs539898848, ExAC 0.02%). This sequence change replaces glycine with arginine at codon 691 of the PYGL protein (p.Gly691Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine.
Neuberg Centre For Genomic Medicine, NCGM	RCV000811116	SCV004176622	likely pathogenic	Glycogen storage disease, type VI	2023-02-14	criteria provided, single submitter	clinical testing	The missense c.2071G>C (p.Gly691Arg) variant in PYGL gene has been reported in compound heterozygous or homozygous state in multiple individuals affected with glycogen storage disorders (Degrassi I, et. al., 2021). This variant is reported with the allele frequency 0.003% in the gnomAD and novel in 1000 genome database. This variant has been reported to the ClinVar database as Pathogenic. The amino acid Gly at position 691 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Gly691Arg in PYGL is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Functional studies are required to prove pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000811116	SCV004809417	likely pathogenic	Glycogen storage disease, type VI	2024-04-04	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000811116	SCV005629303	likely pathogenic	Glycogen storage disease, type VI	2024-02-28	criteria provided, single submitter	clinical testing