ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.359G>T (p.Arg120Leu)

gnomAD frequency: 0.00001  dbSNP: rs775756069
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001887570 SCV002162282 uncertain significance Lethal congenital glycogen storage disease of heart 2022-08-09 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1397115). 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 PRKAG2 protein function. 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. This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 120 of the PRKAG2 protein (p.Arg120Leu). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions.
Ambry Genetics RCV002458750 SCV002617375 uncertain significance Cardiovascular phenotype 2022-09-24 criteria provided, single submitter clinical testing The p.R120L variant (also known as c.359G>T), located in coding exon 3 of the PRKAG2 gene, results from a G to T substitution at nucleotide position 359. The arginine at codon 120 is replaced by leucine, 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.
All of Us Research Program, National Institutes of Health RCV004010805 SCV004836781 uncertain significance Hypertrophic cardiomyopathy 2023-10-02 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 120 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 PRKAG2-related disorders in the literature. This variant has been identified in 1/251228 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.

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