ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.66C>T (p.Gly22=)

gnomAD frequency: 0.00003  dbSNP: rs730880971
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158994 SCV000208935 uncertain significance not provided 2014-02-26 criteria provided, single submitter clinical testing p.Gly22Gly (GGC>GGT): c.66 C>T in exon 1 of the PRKAG2 gene (NM_016203.3) A c.66 C>T variant of unknown significance was identified in the PRKAG2 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.66 C>T variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In silico splice algorithms predict this nucleotide substitution results in a cryptic splice donor site with a higher affinity than the wild-type splice donor site. However, other splice site mutations in the PRKAG2 gene have not been reported.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Color Diagnostics, LLC DBA Color Health RCV001526094 SCV001736370 likely benign Cardiomyopathy 2023-12-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001857572 SCV002288343 uncertain significance Lethal congenital glycogen storage disease of heart 2021-08-26 criteria provided, single submitter clinical testing This sequence change affects codon 22 of the PRKAG2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PRKAG2 protein. This variant is not present in population databases (ExAC no frequency). 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: 181466). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV003998378 SCV004842341 uncertain significance Hypertrophic cardiomyopathy 2023-10-23 criteria provided, single submitter clinical testing This synonymous variant causes a nucleotide substitution but does not change the encoded amino acid at codon 22 of the PRKAG2 protein. Splice site prediction tools are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PRKAG2-related disorders in the literature. This variant has been identified in 2/279206 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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