ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.31A>G (p.Lys11Glu)

gnomAD frequency: 0.00001  dbSNP: rs1041124171
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000623460 SCV000740493 uncertain significance Primary familial hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765950 SCV000897371 uncertain significance Lethal congenital glycogen storage disease of heart; Hypertrophic cardiomyopathy 6; Wolff-Parkinson-White pattern 2018-10-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001179404 SCV001344059 uncertain significance Cardiomyopathy 2023-09-07 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 11 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 been reported in one individual affected with hypertrophic cardiomyopathy (PMID: 33495597). This variant has been identified in 2/280044 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003106003 SCV003783559 uncertain significance Lethal congenital glycogen storage disease of heart 2022-05-06 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 11 of the PRKAG2 protein (p.Lys11Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 520489). 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. 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.
All of Us Research Program, National Institutes of Health RCV004002749 SCV004842349 uncertain significance Hypertrophic cardiomyopathy 2023-11-20 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant replaces lysine with glutamic acid at codon 11 of the PRKAG2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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