Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001203638 | SCV001374812 | uncertain significance | not provided | 2020-08-20 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with HCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 935120). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with histidine at codon 377 of the HCN2 protein (p.Leu377His). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and histidine. |
Department of Genetics, |
RCV003770239 | SCV004697327 | pathogenic | HCN2 related developmental and epileptic encephalopathy | 2024-02-07 | criteria provided, single submitter | research |