Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000635048 | SCV000756426 | uncertain significance | Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV | 2021-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with leucine at codon 1357 of the CACNA1H protein (p.His1357Leu). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and leucine. This variant is present in population databases (rs775971172, ExAC 0.002%). This variant has not been reported in the literature in individuals with CACNA1H-related disease. ClinVar contains an entry for this variant (Variation ID: 529589). 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 C0"). 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. |