ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.1592G>T (p.Arg531Leu) (rs121908991)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038921 SCV000062599 likely pathogenic Hypertrophic cardiomyopathy 2013-01-23 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Invitae RCV000641181 SCV000762819 pathogenic Glycogen storage disease of heart, lethal congenital 2018-06-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 531 of the PRKAG2 protein (p.Arg531Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 25611685, 27532257). ClinVar contains an entry for this variant (Variation ID: 45701). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Two additional missense substitutions at this codon (p.Arg531Gln, p.Arg531Gln) has been determined to be pathogenic (PMID: 15877279, 25611685, 11748095, 14722619, 27621313). This suggests that the arginine residue is critical for PRKAG2 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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