Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000481929 | SCV000569690 | likely pathogenic | not provided | 2016-03-31 | criteria provided, single submitter | clinical testing | A novel c.234_238dupATTTC variant that is likely pathogenic has been identified in the CDKL5 gene. The c.234_238dupATTTC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.234_238dupATTTC variant in the CDKL5 gene causes a frameshift starting with codon Arginine 80, changes this amino acid to a Histidine residue and creates a premature Stop codon at position 35 of the new reading frame, denoted p.R80HfsX35. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Additionally, other frameshift variants have been reported in the CDKL5 gene in association with CDKL5-related disorders (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |