Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001071673 | SCV001236989 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2019-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 2166 of the CACNA1A protein (p.Arg2166Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CACNA1A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV003363104 | SCV004081885 | uncertain significance | Inborn genetic diseases | 2023-07-25 | criteria provided, single submitter | clinical testing | The c.6496C>T (p.R2166C) alteration is located in exon 45 (coding exon 45) of the CACNA1A gene. This alteration results from a C to T substitution at nucleotide position 6496, causing the arginine (R) at amino acid position 2166 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |