Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001244425 | SCV001417645 | uncertain significance | Brugada syndrome 8 | 2025-01-20 | criteria provided, single submitter | clinical testing | This variant, c.483_500dup, results in the insertion of 6 amino acid(s) of the HCN4 protein (p.Ala162_Pro167dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with HCN4-related conditions. ClinVar contains an entry for this variant (Variation ID: 969148). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Gene |
RCV001760278 | SCV001989733 | uncertain significance | not provided | 2019-04-23 | criteria provided, single submitter | clinical testing | In-frame insertion of 6 amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002339676 | SCV002639196 | uncertain significance | Cardiovascular phenotype | 2024-06-18 | criteria provided, single submitter | clinical testing | The c.483_500dup18 variant (also known as p.A162_P167dup) is located in coding exon 1 of the HCN4 gene. This variant results from an in-frame duplication of 18 nucleotides at positions 483 to 500. This results in the duplication of 6 amino acid residues (alanine, alanine, serine, proline, proline, proline) between codons 162 and 167. These amino acid positions are not well conserved in available vertebrate species. This alteration is predicted to be neutral by in silico analysis (Choi Y et al., PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002491818 | SCV002785496 | uncertain significance | Sick sinus syndrome 2, autosomal dominant; Brugada syndrome 8; Epilepsy, idiopathic generalized, susceptibility to, 18 | 2021-10-26 | criteria provided, single submitter | clinical testing | |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV002339676 | SCV006067808 | uncertain significance | Cardiovascular phenotype | 2025-04-09 | criteria provided, single submitter | clinical testing | PM2,PM4_supp |