Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV002510624 | SCV002820110 | uncertain significance | Developmental and epileptic encephalopathy, 1 | criteria provided, single submitter | clinical testing | The missense variant p.L537P in ARX (NM_139058.3) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.L537P variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between leucine and proline. The p.L537P missense variant is predicted to be damaging by both SIFT and PolyPhen2. The leucine residue at codon 537 of ARX is conserved in all mammalian species. The nucleotide c.1610 in ARX is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |