Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004818970 | SCV005438984 | uncertain significance | Developmental and epileptic encephalopathy 99 | criteria provided, single submitter | clinical testing | The missense c.1654G>Ap.Glu552Lys variant in ATP1A3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Glu552Lys variant is present with allele frequency of 0.0004% in gnomAD Exomes. The p.Glu552Lys variant has not been submitted to the ClinVar database. Computational evidence Polyphen - Benign, SIFT - Tolerated and MutationTaster -Disease causing predicts conflicting evidence on protein structure and function for this variant. The reference amino acid at this position is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Glu at position 552 is changed to a Lys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance VUS. |