Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002421755 | SCV002722156 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-01-04 | criteria provided, single submitter | clinical testing | The p.S654T variant (also known as c.1961G>C), located in coding exon 17 of the PRKG1 gene, results from a G to C substitution at nucleotide position 1961. The serine at codon 654 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, threonine is the reference amino acid in other vertebrate species. 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. |
| Labcorp Genetics |
RCV005097856 | SCV005767798 | uncertain significance | Aortic aneurysm, familial thoracic 8 | 2024-03-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 654 of the PRKG1 protein (p.Ser654Thr). This variant is present in population databases (rs759599450, gnomAD 0.002%). 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: 1783446). 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. |