ClinVar Miner

Submissions for variant NM_016203.4(PRKAG2):c.196C>T (p.Pro66Ser)

dbSNP: rs764915841
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001191484 SCV001359306 uncertain significance Cardiomyopathy 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 66 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 1/231670 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002560116 SCV003462254 uncertain significance Lethal congenital glycogen storage disease of heart 2023-05-29 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: 927911). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. This variant is present in population databases (rs764915841, gnomAD 0.001%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 66 of the PRKAG2 protein (p.Pro66Ser).
Ambry Genetics RCV004033429 SCV005026395 uncertain significance Cardiovascular phenotype 2023-11-01 criteria provided, single submitter clinical testing The p.P66S variant (also known as c.196C>T), located in coding exon 3 of the PRKAG2 gene, results from a C to T substitution at nucleotide position 196. The proline at codon 66 is replaced by serine, an amino acid with similar 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.

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