Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002925672 | SCV003666654 | uncertain significance | Inborn genetic diseases | 2022-12-15 | criteria provided, single submitter | clinical testing | The c.5956C>G (p.L1986V) alteration is located in exon 41 (coding exon 41) of the CACNA1A gene. This alteration results from a C to G substitution at nucleotide position 5956, causing the leucine (L) at amino acid position 1986 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003777975 | SCV004584226 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1986 of the CACNA1A protein (p.Leu1986Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 2335100). 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 with a negative predictive value of 95%. 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. |