Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001344875 | SCV001538959 | uncertain significance | Brugada syndrome 8 | 2020-01-30 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). This variant has not been reported in the literature in individuals with HCN4-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces glutamine with arginine at codon 1081 of the HCN4 protein (p.Gln1081Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. |
Ambry Genetics | RCV002322288 | SCV002609472 | uncertain significance | Cardiovascular phenotype | 2022-06-22 | criteria provided, single submitter | clinical testing | The p.Q1081R variant (also known as c.3242A>G), located in coding exon 8 of the HCN4 gene, results from an A to G substitution at nucleotide position 3242. The glutamine at codon 1081 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002493767 | SCV002775244 | uncertain significance | Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 | 2021-07-12 | criteria provided, single submitter | clinical testing |