ClinVar Miner

Submissions for variant NM_001291415.2(KDM6A):c.1214C>T (p.Pro405Leu)

dbSNP: rs1556309489
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519188 SCV000620272 uncertain significance not provided 2017-08-22 criteria provided, single submitter clinical testing The P405L variant in the KDM6A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P405L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P405L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P405L as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003114652 SCV003784677 uncertain significance Kabuki syndrome 2 2023-03-29 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 405 of the KDM6A protein (p.Pro405Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KDM6A-related conditions. ClinVar contains an entry for this variant (Variation ID: 451553). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KDM6A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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