ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.679A>G (p.Lys227Glu)

gnomAD frequency: 0.00001  dbSNP: rs766460601
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000821713 SCV000962482 uncertain significance Lethal congenital glycogen storage disease of heart 2018-10-11 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PRKAG2-related disease. This variant is present in population databases (rs766460601, ExAC 0.003%). This sequence change replaces lysine with glutamic acid at codon 227 of the PRKAG2 protein (p.Lys227Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid.
Color Diagnostics, LLC DBA Color Health RCV003532281 SCV004359753 uncertain significance Cardiomyopathy 2022-04-25 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 227 of the PRKAG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 2/250816 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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