ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.1625T>C (p.Val542Ala)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002401145 SCV002708947 uncertain significance Cardiovascular phenotype 2021-02-24 criteria provided, single submitter clinical testing The p.V542A variant (also known as c.1625T>C), located in coding exon 15 of the PRKAG2 gene, results from a T to C substitution at nucleotide position 1625. The valine at codon 542 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003097025 SCV003247738 uncertain significance Lethal congenital glycogen storage disease of heart 2022-07-04 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 542 of the PRKAG2 protein (p.Val542Ala). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. This variant is present in population databases (rs757047965, gnomAD 0.006%).
All of Us Research Program, National Institutes of Health RCV004007343 SCV004829114 uncertain significance Hypertrophic cardiomyopathy 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces valine with alanine at codon 542 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). 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 2/251482 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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