Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000520510 | SCV000621767 | uncertain significance | not provided | 2017-10-18 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PRKG1 gene. The C190R variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is also not observed in large population cohorts (Lek et al., 2016). The C190R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Of note, this substitution is located within the cGMP Binding Domain near the recurrent gain-of-function R177Q variant (described as R192Q in the NM_006258.3 transcript) that has been reported in association with ascending and descending aortic aneurysm/dissection (Guo et al., 2013; Gago-Diaz et al., 2016). However, this variant has not been observed in a significant number of affected individuals, and it lacks both segregation and functional studies which would further clarify its pathogenicity. |
| Labcorp Genetics |
RCV005091248 | SCV005790311 | uncertain significance | Aortic aneurysm, familial thoracic 8 | 2024-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 190 of the PRKG1 protein (p.Cys190Arg). This variant is not present in population databases (gnomAD no frequency). 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: 452918). 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 disruptive. 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. |