Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002318193 | SCV000851445 | uncertain significance | Inborn genetic diseases | 2017-01-12 | criteria provided, single submitter | clinical testing | The p.Y2082H variant (also known as c.6244T>C), located in coding exon 43 of the CACNA1A gene, results from a T to C substitution at nucleotide position 6244. The tyrosine at codon 2082 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003768159 | SCV004587190 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 2082 of the CACNA1A protein (p.Tyr2082His). 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: 590008). 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. 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. |