Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002315449 | SCV000849350 | uncertain significance | Inborn genetic diseases | 2017-04-13 | criteria provided, single submitter | clinical testing | The p.G411W variant (also known as c.1231G>T), located in coding exon 9 of the CACNA1A gene, results from a G to T substitution at nucleotide position 1231. The glycine at codon 411 is replaced by tryptophan, an amino acid with highly dissimilar properties. This variant has been reported in an individual with nystagmus (Maksemous N et al. Mol Genet Genomic Med, 2016 Mar;4:211-22). This amino acid position is not 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. |
Gene |
RCV001759434 | SCV001987869 | uncertain significance | not provided | 2020-11-16 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27066515, 32899500, 32116539) |
Invitae | RCV001862049 | SCV002180360 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2023-06-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 588956). 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. This missense change has been observed in individual(s) with episodic ataxia type 2 (PMID: 27066515). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 411 of the CACNA1A protein (p.Gly411Trp). |
Revvity Omics, |
RCV001759434 | SCV003830262 | uncertain significance | not provided | 2023-10-03 | criteria provided, single submitter | clinical testing |