ClinVar Miner

Submissions for variant NM_006258.4(PRKG1):c.299C>G (p.Pro100Arg)

gnomAD frequency: 0.00002  dbSNP: rs763629518
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001768743 SCV001992616 uncertain significance not provided 2025-01-13 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function
Phosphorus, Inc. RCV001823789 SCV002073460 uncertain significance not specified 2022-01-18 criteria provided, single submitter clinical testing This missense variant results in an amino acid substitution of Proline with Arginine at codon 100 of the PRKG1 gene (transcript: NM_006258.3). This variant has an entry in ClinVar (1305536) NM_006258.4(PRKG1):c.299C>G (p.Pro100Arg). This variant occurred in gnomAD with a total MAF of 0.0012% and with the highest MAF of 0.0028% in the European population. This position is conserved. In silico functional algorithms predict this variant to be benign (PolyPhen) and tolerated (SIFT). However, no functional studies were performed to confirm either of those predictions. The variant has not occurred in the literature in association with the disease. Considering that this is a rare variant and the available evidence is not enough to ascertain its role in disease, it has been classified as Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002032834 SCV002198431 uncertain significance Aortic aneurysm, familial thoracic 8 2024-10-31 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 100 of the PRKG1 protein (p.Pro100Arg). This variant is present in population databases (rs763629518, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PRKG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1305536). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV003375351 SCV004095962 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-06-22 criteria provided, single submitter clinical testing The p.P100R variant (also known as c.299C>G), located in coding exon 1 of the PRKG1 gene, results from a C to G substitution at nucleotide position 299. The proline at codon 100 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.

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