ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.148G>A (p.Gly50Arg)

gnomAD frequency: 0.00001  dbSNP: rs1430071393
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001231860 SCV001404395 uncertain significance Lethal congenital glycogen storage disease of heart 2024-09-17 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 50 of the PRKAG2 protein (p.Gly50Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 958655). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PRKAG2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004033140 SCV003965309 uncertain significance Cardiovascular phenotype 2023-03-31 criteria provided, single submitter clinical testing The c.148G>A (p.G50R) alteration is located in exon 2 (coding exon 2) of the PRKAG2 gene. This alteration results from a G to A substitution at nucleotide position 148, causing the glycine (G) at amino acid position 50 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004528428 SCV004111118 uncertain significance PRKAG2-related disorder 2023-07-24 criteria provided, single submitter clinical testing The PRKAG2 c.148G>A variant is predicted to result in the amino acid substitution p.Gly50Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV004004838 SCV004821540 uncertain significance Hypertrophic cardiomyopathy 2023-08-28 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 50 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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.

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