Submissions for variant NM_005609.4(PYGM):c.2392T>C (p.Trp798Arg)

dbSNP: rs119103258

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081312	SCV000227678	pathogenic	not provided	2012-07-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000081312	SCV000491226	pathogenic	not provided	2024-04-29	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as W797R; This variant is associated with the following publications: (PMID: 19251976, 10590419, 17221871, 10681080, 11706962, 20301518, 29143597, 17994553, 14722619, 11168025, 29926259, 32560448, 33370875, 31589614, 30415384, 34534370, 22250184, 34598035)
Counsyl	RCV000002402	SCV000677925	pathogenic	Glycogen storage disease, type V	2015-07-29	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000002402	SCV000803466	likely pathogenic	Glycogen storage disease, type V	2018-05-31	criteria provided, single submitter	curation	This variant is interpreted as a Likely Pathogenic, for Glycogen storage disease 5, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Common mutation observed in multiple unrelated patients. (PMID:10590419,29143597,/10681080,14722619). PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:29143597). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product.
Fulgent Genetics, Fulgent Genetics	RCV000002402	SCV000893903	pathogenic	Glycogen storage disease, type V	2021-11-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000002402	SCV001580144	pathogenic	Glycogen storage disease, type V	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 798 of the PYGM protein (p.Trp798Arg). This variant is present in population databases (rs119103258, gnomAD 0.006%). This missense change has been observed in individual(s) with McArdle disease (PMID: 10590419, 10681080, 17994553, 22250184, 30415384). This variant is also known as W797R. ClinVar contains an entry for this variant (Variation ID: 2312). 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 PYGM protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000002402	SCV002019580	pathogenic	Glycogen storage disease, type V	2021-09-28	criteria provided, single submitter	clinical testing
DASA	RCV000002402	SCV002061163	pathogenic	Glycogen storage disease, type V	2022-01-05	criteria provided, single submitter	clinical testing	The c.2392T>C;p.(Trp798Arg) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 2312; PMID: 10590419;30415384;17994553;22250184;10681080) - PS4.The variant is located in a mutational hot spot and/or critical and well-established functional domain (Phosphorylase domain) - PM1. The variant is present at low allele frequencies population databases (rs119103258– gnomAD 0.00001979%; ABraOM 0.001281 frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Trp798Arg) was detected in trans with a pathogenic variant (PMID: 10590419; 30415384; 17994553; 22250184; 10681080) - PM3 Pathogenic missense variant in this residue have been reported (ClinVar ID: 526617) - PM5. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000002402	SCV002570794	pathogenic	Glycogen storage disease, type V	2022-07-14	criteria provided, single submitter	clinical testing	Variant summary: PYGM c.2392T>C (p.Trp798Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251496 control chromosomes. c.2392T>C has been widely reported in the literature in multiple individuals affected with Glycogen Storage Disease, Type V (example, Lucia_2007, Vieitez_2011). These data indicate that the variant is very likely to be associated with disease. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV000002402	SCV004207243	pathogenic	Glycogen storage disease, type V	2024-03-28	criteria provided, single submitter	clinical testing
OMIM	RCV000002402	SCV000022560	pathogenic	Glycogen storage disease, type V	2001-01-01	no assertion criteria provided	literature only
GeneReviews	RCV000002402	SCV000172201	not provided	Glycogen storage disease, type V		no assertion provided	literature only
Natera, Inc.	RCV000002402	SCV001461268	pathogenic	Glycogen storage disease, type V	2020-09-16	no assertion criteria provided	clinical testing