Submissions for variant NM_016203.4(PRKAG2):c.454C>T (p.Arg152Cys)

gnomAD frequency: 0.00002  dbSNP: rs752783859

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001181711	SCV001346905	uncertain significance	Cardiomyopathy	2023-04-05	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with cysteine at codon 152 of the PRKAG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with an unknown arrhythmia (PMID: 30847666). This variant has been identified in 7/251168 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001340952	SCV001534786	likely benign	Lethal congenital glycogen storage disease of heart	2024-05-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002332574	SCV002634205	uncertain significance	Cardiovascular phenotype	2021-06-29	criteria provided, single submitter	clinical testing	The p.R152C variant (also known as c.454C>T), located in coding exon 3 of the PRKAG2 gene, results from a C to T substitution at nucleotide position 454. The arginine at codon 152 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was reported in a cardiac genetic testing cohort in one individual; however, clinical details were limited (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001181711	SCV003838479	uncertain significance	Cardiomyopathy	2021-06-04	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004001544	SCV004842294	uncertain significance	Hypertrophic cardiomyopathy	2024-07-29	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with cysteine at codon 152 of the PRKAG2 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 7/251168 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000786198	SCV000924908	uncertain significance	not provided	2017-03-20	no assertion criteria provided	provider interpretation