Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000418568 | SCV000529158 | uncertain significance | not provided | 2016-06-27 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CACNA1A gene. The R813Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R813Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a conserved position predicted to be within the cytoplasmic loop between the second and third homologous domains. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000821566 | SCV000962328 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2022-11-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 813 of the CACNA1A protein (p.Arg813Gln). ClinVar contains an entry for this variant (Variation ID: 387225). 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. |