Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV003337912 | SCV004048335 | uncertain significance | Developmental and epileptic encephalopathy, 2 | criteria provided, single submitter | clinical testing | The missense variant c.103A>G (p.Thr35Ala) in CDKL5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge The p.Thr35Ala variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Thr at position 35 is changed to a Ala changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Thr35Ala in CDKL5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS). The above variant has been detected in a heterozygous state (alt allele -29%) as opposed to the expected hemizygous state. This could indicate the possibility of the variant being present in a mosaic state. |