Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001850014 | SCV002132199 | pathogenic | Dystonia 12 | 2021-11-22 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with alternating hemiplegia of childhood (PMID: 22850527, 27146299). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 18 of the ATP1A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATP1A3 are known to be pathogenic (PMID: 24631656, 24983657). ClinVar contains an entry for this variant (Variation ID: 161145). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |
OMIM | RCV000148326 | SCV000267140 | pathogenic | Alternating hemiplegia of childhood 2 | 2012-09-01 | no assertion criteria provided | literature only |