ClinVar Miner

Submissions for variant NM_001291415.2(KDM6A):c.4339C>G (p.Pro1447Ala)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004628436 SCV005127604 uncertain significance Inborn genetic diseases 2024-04-17 criteria provided, single submitter clinical testing The c.4183C>G (p.P1395A) alteration is located in exon 29 (coding exon 29) of the KDM6A gene. This alteration results from a C to G substitution at nucleotide position 4183, causing the proline (P) at amino acid position 1395 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004818793 SCV005439678 uncertain significance not provided 2024-06-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV005102247 SCV005770926 uncertain significance Kabuki syndrome 2 2025-01-01 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1395 of the KDM6A protein (p.Pro1395Ala). 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. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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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