ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.1238C>G (p.Ser413Cys)

gnomAD frequency: 0.00001  dbSNP: rs758756757
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176928 SCV001341029 uncertain significance Cardiomyopathy 2023-03-15 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 413 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 3/251480 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 RCV002365844 SCV002662732 uncertain significance Cardiovascular phenotype 2022-09-12 criteria provided, single submitter clinical testing The p.S413C variant (also known as c.1238C>G), located in coding exon 12 of the PRKAG2 gene, results from a C to G substitution at nucleotide position 1238. The serine at codon 413 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002497618 SCV002816019 uncertain significance Lethal congenital glycogen storage disease of heart; Hypertrophic cardiomyopathy 6; Wolff-Parkinson-White pattern 2021-08-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002559707 SCV003268935 uncertain significance Lethal congenital glycogen storage disease of heart 2022-04-12 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRKAG2 protein function. ClinVar contains an entry for this variant (Variation ID: 919004). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. This variant is present in population databases (rs758756757, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 413 of the PRKAG2 protein (p.Ser413Cys).
All of Us Research Program, National Institutes of Health RCV004006338 SCV004842224 uncertain significance Hypertrophic cardiomyopathy 2023-12-07 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 413 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 3/251480 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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