Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002037295 | SCV002115411 | likely pathogenic | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2021-04-23 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 1862 of the CACNA1A protein (p.Pro1862Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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"). This variant has been observed in individual(s) with clinical features of CACNA1A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. |