Submissions for variant NM_016203.4(PRKAG2):c.433G>A (p.Gly145Arg)

gnomAD frequency: 0.00002  dbSNP: rs886062101

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000367717	SCV000467639	uncertain significance	Hypertrophic cardiomyopathy 6	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000328054	SCV000467641	uncertain significance	Wolff-Parkinson-White pattern	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	RCV000367717	SCV000996336	uncertain significance	Hypertrophic cardiomyopathy 6	2017-03-17	criteria provided, single submitter	research	The PRKAG2 Gly145Arg variant is absent from the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/) and is present at a low frequency in the Genome Aggregation Database (MAF=0.0000079, http://gnomad.broadinstitute.org/). We identified this variant in a patient with a HCM and ECG highly suggestive of Wolff-Parkinson-White (WPW) Syndrome. The variant was the variant segregated to the patient first degree relative who has mild concentric hypertrophy. Computational tools PolyPhen-2 and MutationTaster predict this variant to be deleterious, however SIFT predicts this variant to be "tolerated". In summary, the variant is rare in the general population, however there is no further information available at this time to classify the variant as either pathogenic or benign, therefore we classify PRKAG2 Gly145Arg as a variant of "uncertain significance".
Labcorp Genetics (formerly Invitae), Labcorp	RCV002524527	SCV003506594	likely benign	Lethal congenital glycogen storage disease of heart	2024-01-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003168557	SCV003864601	uncertain significance	Cardiovascular phenotype	2022-11-27	criteria provided, single submitter	clinical testing	The p.G145R variant (also known as c.433G>A), located in coding exon 3 of the PRKAG2 gene, results from a G to A substitution at nucleotide position 433. The glycine at codon 145 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.