ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.254C>A (p.Pro85His)

gnomAD frequency: 0.00002  dbSNP: rs753496711
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002927453 SCV003260030 uncertain significance Lethal congenital glycogen storage disease of heart 2021-12-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 85 of the PRKAG2 protein (p.Pro85His). This variant is present in population databases (rs753496711, gnomAD 0.003%). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions.
All of Us Research Program, National Institutes of Health RCV004007689 SCV004815723 uncertain significance Hypertrophic cardiomyopathy 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces proline with histidine at codon 85 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 not been reported in individuals affected with PRKAG2-related disorders in the literature. This variant has been identified in 4/276716 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.
Ambry Genetics RCV004066312 SCV005011586 uncertain significance Cardiovascular phenotype 2025-02-10 criteria provided, single submitter clinical testing The p.P85H variant (also known as c.254C>A), located in coding exon 3 of the PRKAG2 gene, results from a C to A substitution at nucleotide position 254. The proline at codon 85 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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