Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001948861 | SCV002213036 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2021-08-08 | criteria provided, single submitter | clinical testing | 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 leucine at codon 2238 of the CACNA1A protein (p.Arg2238Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine. This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. 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. 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 CACNA1A protein function. |