ClinVar Miner

Submissions for variant NM_006258.4(PRKG1):c.2052A>G (p.Ile684Met)

gnomAD frequency: 0.00001  dbSNP: rs374752370
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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 RCV001348907 SCV001543233 uncertain significance Aortic aneurysm, familial thoracic 8 2024-04-06 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 684 of the PRKG1 protein (p.Ile684Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1044634). 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.
GeneDx RCV003318683 SCV004022729 uncertain significance not provided 2023-07-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004036568 SCV005025168 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-11-17 criteria provided, single submitter clinical testing The p.I684M variant (also known as c.2052A>G), located in coding exon 18 of the PRKG1 gene, results from an A to G substitution at nucleotide position 2052. The isoleucine at codon 684 is replaced by methionine, an amino acid with highly 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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