ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.712G>A (p.Ala238Thr)

gnomAD frequency: 0.00051  dbSNP: rs200736454
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000786197 SCV000208929 likely benign not provided 2020-12-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001088403 SCV000290216 likely benign Lethal congenital glycogen storage disease of heart 2025-01-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000622232 SCV000739920 likely benign Cardiovascular phenotype 2018-04-24 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170703 SCV001333297 benign Cardiomyopathy 2019-02-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001170703 SCV001339602 likely benign Cardiomyopathy 2019-08-22 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 238 of the PRKAG2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. 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 27/192420 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.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786197 SCV000924907 uncertain significance not provided 2016-06-21 no assertion criteria provided provider interpretation Given the lack of case data and relatively high frequency in ethnicity-matched controls we consider this variant to be uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has not been reported in the literature. We have seen this variant in an individual with LVNC. The Invitae report notes: The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. Please note that this site is covered in fewer than 80% of the individuals in Exac, and may represent a low quality site. The variant was reported online in 12 of 40,075 (0.2%) individuals in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of 4/2016). Specifically, the variant was observed in 12 of 2461 (0.4%) people of African descent. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease
PreventionGenetics, part of Exact Sciences RCV004734751 SCV005350699 likely benign PRKAG2-related disorder 2024-08-12 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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