Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000820080 | SCV000960774 | uncertain significance | Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV | 2020-08-25 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with CACNA1H-related conditions. ClinVar contains an entry for this variant (Variation ID: 662438). 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 arginine with histidine at codon 1189 of the CACNA1H protein (p.Arg1189His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. |
| Fulgent Genetics, |
RCV002478918 | SCV002778091 | uncertain significance | Epilepsy, childhood absence, susceptibility to, 6; Hyperaldosteronism, familial, type IV | 2022-01-18 | criteria provided, single submitter | clinical testing |