Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002029408 | SCV002305542 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2020-11-16 | 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. This variant disrupts the p.Asp401 amino acid residue in HCN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24747641). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 C15"). This variant has been observed in individual(s) with clinical features of HCN1-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with asparagine at codon 401 of the HCN1 protein (p.Asp401Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. |
| Gene |
RCV004785458 | SCV005401712 | likely pathogenic | not provided | 2024-05-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |