ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.526T>A (p.Trp176Arg) (rs587783084)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000144746 SCV000190957 likely pathogenic not provided 2012-06-04 criteria provided, single submitter clinical testing The Trp176Arg missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Trp176Arg in approximately 5,000 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as an uncharged non-polar Tryptophan residue is replaced by a positively charged Arginine residue. Trp176Arg alters a highly conserved residue in the activation loop of the catalytic domain of the protein, and mutations have been reported at many neighboring codons, confirming the functional importance of the region (Bertani et al., 2006). Additionally, multiple in silico models predict that Trp176Arg is damaging to protein structure/function. Therefore, Trp176Arg is a strong candidate as a disease-causing mutation; however, the possibility that it is a benign variant cannot be completely excluded at this time. The variant is found in EPILEPSY panel(s).

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