Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000657849 | SCV000779606 | uncertain significance | not provided | 2018-05-23 | criteria provided, single submitter | clinical testing | A second variant of uncertain significance has been identified in the CACNA1H gene. The G2241R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G2241R variant is observed in 1/8990 (0.01%) alleles from individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). The G2241R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001855360 | SCV002184736 | uncertain significance | Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV | 2023-03-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2241 of the CACNA1H protein (p.Gly2241Arg). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. ClinVar contains an entry for this variant (Variation ID: 546071). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1H protein function. 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. |
| Fulgent Genetics, |
RCV002477471 | SCV002783469 | uncertain significance | Epilepsy, childhood absence, susceptibility to, 6; Hyperaldosteronism, familial, type IV | 2022-03-25 | criteria provided, single submitter | clinical testing | |
| Breakthrough Genomics, |
RCV000657849 | SCV005194086 | uncertain significance | not provided | criteria provided, single submitter | not provided |