Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001044273 | SCV001208063 | uncertain significance | Brugada syndrome 8 | 2019-12-12 | criteria provided, single submitter | clinical testing | 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 proline with histidine at codon 943 of the HCN4 protein (p.Pro943His). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and histidine. This variant has not been reported in the literature in individuals with HCN4-related conditions. 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. |
Ambry Genetics | RCV002436567 | SCV002752244 | uncertain significance | Cardiovascular phenotype | 2025-03-04 | criteria provided, single submitter | clinical testing | The c.2828C>A (p.P943H) alteration is located in exon 8 (coding exon 8) of the HCN4 gene. This alteration results from a C to A substitution at nucleotide position 2828, causing the proline (P) at amino acid position 943 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |