Submissions for variant NM_016203.4(PRKAG2):c.251G>A (p.Arg84Gln)

gnomAD frequency: 0.00036  dbSNP: rs201953758

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038933	SCV000062611	uncertain significance	not specified	2012-12-11	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Arg84Gln varian t in PRKAG2 has not been reported in the literature, but has been identified in 2 Caucasian individuals with HCM tested by our laboratory, one of which carried a second pathogenic variant sufficient to explain disease. Arginine (Arg) at pos ition 84 is not completely conserved in mammals and several species (elephant, r ock hyrax, and tenrec) carry a glutamine (Gln; this variant), supporting that th is change may be tolerated. Additional computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) also suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Finally, this variant is outside the CBS domain (residu es 277-555) where all pathogenic PRKAG2 variants identified to date are located. In summary, the available information on the Arg84Gln variant supports that it may be benign, but additional studies are needed to fully assess its clinical si gnificance.
GeneDx	RCV001719755	SCV000208967	likely benign	not provided	2020-05-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000464971	SCV000561807	likely benign	Lethal congenital glycogen storage disease of heart	2025-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000618885	SCV000740027	likely benign	Cardiovascular phenotype	2018-09-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV000771891	SCV000904653	likely benign	Cardiomyopathy	2018-10-29	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000771891	SCV002043489	benign	Cardiomyopathy	2020-11-19	criteria provided, single submitter	clinical testing