ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.393T>G (p.Ile131Met)

dbSNP: rs1085307934
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489913 SCV000577687 likely pathogenic not provided 2015-07-15 criteria provided, single submitter clinical testing The I131M variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism 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 I131M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (C126Y; H127Y/R; V132G) have been reported in the Human Gene Mutation Database in association with CDKL5-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.

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