Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181764 | SCV000234067 | uncertain significance | not provided | 2018-08-13 | criteria provided, single submitter | clinical testing | p.Gly224Arg (GGG>AGG): c.670 G>A in exon 4 of the KCNH2 gene (NM_000238.2)A variant of unknown significance has been identified in the KCNH2 gene. The G224R variant has not been published as a mutation or as a benign polymorphism to our knowledge. The G224R variant was not observed in approximately 5,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, the G224R 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. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function, however at least two models predict this variant is possibly damaging to the protein structure/function. One missense mutation in a nearby residue (M218V) has been reported in association with LQTS, supporting the functional importance of this region of the protein.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in LQT panel(s). |
| Athena Diagnostics | RCV000181764 | SCV001144315 | uncertain significance | not provided | 2019-07-03 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002503707 | SCV002816234 | uncertain significance | Short QT syndrome type 1; Long QT syndrome 2 | 2021-09-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004629158 | SCV005122573 | uncertain significance | Cardiovascular phenotype | 2024-05-09 | criteria provided, single submitter | clinical testing | The p.G224R variant (also known as c.670G>A), located in coding exon 4 of the KCNH2 gene, results from a G to A substitution at nucleotide position 670. The glycine at codon 224 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |