Submissions for variant NM_016203.4(PRKAG2):c.590C>G (p.Pro197Arg)

dbSNP: rs368637364

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000414843	SCV000492907	uncertain significance	Webbed neck; Coronary artery disorder; Left ventricular hypertrophy; Ventricular tachycardia; Hypertensive disorder; Stroke disorder	2014-09-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000798522	SCV000938142	uncertain significance	Lethal congenital glycogen storage disease of heart	2024-03-07	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 197 of the PRKAG2 protein (p.Pro197Arg). This variant is present in population databases (rs368637364, gnomAD 0.0009%). 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: 374128). 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 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197920	SCV001368703	uncertain significance	Wolff-Parkinson-White pattern	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3.
Mayo Clinic Laboratories, Mayo Clinic	RCV001508228	SCV001714258	uncertain significance	not provided	2020-02-27	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995933	SCV004827215	uncertain significance	Hypertrophic cardiomyopathy	2023-06-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV005402911	SCV006064663	uncertain significance	Cardiomyopathy	2024-07-03	criteria provided, single submitter	clinical testing	This missense variant replaces proline with arginine at codon 197 of the PRKAG2 protein. Computational prediction tools indicate that this variant's impact on protein structure and function is inconclusive. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 37198425). This variant has been identified in 1/251454 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.