Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000529332 | SCV000656805 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2022-04-01 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 476277). 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 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 249 of the CACNA1A protein (p.Met249Val). |
| Ambry Genetics | RCV002384251 | SCV002671711 | uncertain significance | Inborn genetic diseases | 2017-08-07 | criteria provided, single submitter | clinical testing | The p.M249V variant (also known as c.745A>G), located in coding exon 5 of the CACNA1A gene, results from an A to G substitution at nucleotide position 745. The methionine at codon 249 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |