ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.113C>T (p.Pro38Leu)

gnomAD frequency: 0.00002  dbSNP: rs984007665
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001192150 SCV001360133 uncertain significance Cardiomyopathy 2019-12-02 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 38 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/276176 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.
Invitae RCV001347678 SCV001541951 uncertain significance Lethal congenital glycogen storage disease of heart 2022-04-28 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 38 of the PRKAG2 protein (p.Pro38Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 928333). 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. 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.
Ambry Genetics RCV003293977 SCV003997320 uncertain significance Cardiovascular phenotype 2023-04-01 criteria provided, single submitter clinical testing The p.P38L variant (also known as c.113C>T), located in coding exon 1 of the PRKAG2 gene, results from a C to T substitution at nucleotide position 113. The proline at codon 38 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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