Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000697012 | SCV000825601 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2021-02-08 | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CACNA1A-related disease. This variant is present in population databases (rs369920914, ExAC 0.01%). This sequence change replaces lysine with asparagine at codon 472 of the CACNA1A protein (p.Lys472Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. |