Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001203175 | SCV001374327 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2019-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 2135 of the CACNA1A protein (p.Arg2135His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. While this variant is present in population databases (rs749172043), the frequency information is 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: "Tolerated"; 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. |