Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003356916 | SCV004076626 | pathogenic | Inborn genetic diseases | 2023-06-28 | criteria provided, single submitter | clinical testing | The c.2425G>C (p.A809P) alteration is located in exon 18 (coding exon 18) of the ATP1A3 gene. This alteration results from a G to C substitution at nucleotide position 2425, causing the alanine (A) at amino acid position 809 to be replaced by a proline (P). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was reported de novo in multiple individuals with features consistent with ATP1A3-related neurologic disorders (Zech, 2020; Boonsimma, 2020; Dzinovic, 2022). Another alteration at the same codon, c.2426C>A (p.A809D), has been reported de novo in an individual with childhood epilepsy (Yao, 2021). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. |