Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001363049 | SCV001559133 | uncertain significance | Brugada syndrome 8 | 2023-06-28 | criteria provided, single submitter | clinical testing | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HCN4 protein function. ClinVar contains an entry for this variant (Variation ID: 1054529). This variant has not been reported in the literature in individuals affected with HCN4-related conditions. This variant is present in population databases (rs774060688, gnomAD 0.01%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 358 of the HCN4 protein (p.Ile358Thr). |
| Ambry Genetics | RCV002420796 | SCV002721555 | uncertain significance | Cardiovascular phenotype | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.I358T variant (also known as c.1073T>C), located in coding exon 2 of the HCN4 gene, results from a T to C substitution at nucleotide position 1073. The isoleucine at codon 358 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |